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OPINION STATEMENT: Low grade serous carcinoma of the ovary has been delineated as a separate entity from its counterpart high grade serous carcinoma of the ovary. Molecular profiling has helped to further characterize this disease process and has led to new and exciting treatment options. Surgery has always been a cornerstone of management both in primary and recurrent disease settings. Chemotherapy has been a long-standing backbone of adjuvant treatment, but its efficacy continues to be questioned. Hormonal therapy for upfront and recurrent disease is an effective treatment option with a high response rate and minimal side effects. Newer therapies including MEK, CDK 4/6, and PI3KCA inhibitors have emerged as exciting options for recurrent disease. Ongoing clinical trials will hopefully lead to additional therapeutic opportunities based on novel biomarkers in this disease.
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Cistadenocarcinoma Seroso , Terapia Molecular Dirigida , Clasificación del Tumor , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Terapia Molecular Dirigida/métodos , Cistadenocarcinoma Seroso/tratamiento farmacológico , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/terapia , Resultado del Tratamiento , Terapia Combinada/efectos adversos , Manejo de la Enfermedad , Biomarcadores de Tumor , Estadificación de Neoplasias , Ensayos Clínicos como AsuntoRESUMEN
Pediatric and adolescent ovarian lesions are common and are frequently managed by both pediatric surgeons and pediatric and adolescent gynecologists. During the 2023 American Academy of Pediatric Section on Surgery meeting, an educational symposium was delivered focusing on various aspects of management of pediatric and adolescent benign and malignant masses, borderline lesions, and fertility options for children and adolescents undergoing cancer therapies. This article highlights the discussion during this symposium.
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Ginecología , Neoplasias Ováricas , Humanos , Adolescente , Femenino , Niño , Neoplasias Ováricas/terapia , Neoplasias Ováricas/cirugía , Preservación de la Fertilidad/métodos , Pediatría , Grupo de Atención al Paciente , Comunicación Interdisciplinaria , Enfermedades del Ovario/cirugía , Enfermedades del Ovario/terapiaRESUMEN
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Authors. The authors have independently identified an error in the formula that was utilized to calculate the Quality Adjusted Life Years which invalidates the data and the conclusion of the paper. The authors have contacted the journal requesting to retract the article. Apologies are offered to the readers of the journal for any confusion or inconvenience that may have resulted from the publication of this article.
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Protocolos de Quimioterapia Combinada Antineoplásica , Análisis Costo-Beneficio , Neoplasias Endometriales , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/economía , Recurrencia Local de Neoplasia/economía , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/economía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Anciano , Anticuerpos Monoclonales Humanizados/economía , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Años de Vida Ajustados por Calidad de VidaRESUMEN
Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.
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Neoplasias de la Vulva , Femenino , Humanos , Adenocarcinoma/patología , Neoplasias de los Genitales Femeninos , Enfermedad de Paget Extramamaria/diagnóstico , Enfermedad de Paget Extramamaria/etiología , Enfermedad de Paget Extramamaria/terapia , Neoplasias Cutáneas , Neoplasias de la Vulva/diagnóstico , Neoplasias de la Vulva/epidemiología , Neoplasias de la Vulva/etiologíaRESUMEN
OBJECTIVES: The use of a platinum doublet for the treatment of platinum-sensitive epithelial ovarian cancer (EOC) recurrence is well established. The impact of the nonplatinum chemotherapy used as part of a platinum doublet on PARP inhibitor (PARPi) and platinum sensitivity it not known. We aimed to describe oncologic outcomes in cases of recurrent EOC receiving PARPi as maintenance therapy based on preceding platinum doublet. METHODS: Retrospective study of patients with platinum-sensitive recurrent ovarian, fallopian tube or primary peritoneal cancer treated with platinum doublet followed by maintenance PARPi from 1/1/2015 and 1/1/2022. Comparisons were made between patients receiving carboplatin + pegylated liposomal doxorubicin (CD) versus other platinum doublets (OPDs). Descriptive statistics, Kaplan-Meier and univariate survival analyses were performed. RESULTS: 100 patients received PARPi maintenance following a platinum doublet chemotherapy regimen for platinum-sensitive recurrence. 25/100 (25%) received CD and 75/100 (75%) received OPDs. Comparing CD and OPDs, median progression-free survival was 8 versus 7 months (p = 0.26), median time to platinum resistance was 15 versus 13 months (p = 0.54), median OS was 64 versus 90 months (p = 0.28), and median OS from starting PARPi was 25 versus 26 months (p = 0.90), respectively. CONCLUSIONS: Using pegylated liposomal doxorubicin as part of a platinum doublet preceding maintenance PARPi for platinum-sensitive recurrence does not seem to hasten PARPi resistance or platinum resistance compared to OPDs. Although there was a non-significant trend towards increased OS among patients who received a platinum doublet other than CD prior to PARPi, the OS from PARPi start was similar between groups. Given the retrospective nature of this study and small study population, further research is needed to evaluate if the choice of platinum doublet preceding PARPi maintenance impacts PARPi resistance, platinum resistance and survival.
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Doxorrubicina/análogos & derivados , Neoplasias Ováricas , Humanos , Femenino , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Estudios Retrospectivos , Platino (Metal)/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , PolietilenglicolesRESUMEN
The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/terapia , Neoplasias del Cuello Uterino/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
The Society of Gynecologic Oncology (SGO) Journal Club webinar series is an open forum that invites national experts to discuss the literature pertaining to important topics in the management of gynecologic cancers. On August 14th, 2023, SGO hosted a journal club focused on the management of upfront and recurrent vulvar cancer. Our discussants included Dr. Brian M Slomovitz from Mount Sinai Medical Center in Miami Beach, Dr. Emi Yoshida from the University of California San Francisco Helen Diller Family Comprehensive Cancer Center, and Dr. Lilian Gien from the University of Toronto Sunnybrook Odette Cancer Center. During the discussion,we reviewed the progression of vulvar cancer surgery from en bloc resection of the vulva and groins, to partial radical vulvectomy and sentinel lymph nodes. We also reviewed the management of node positive vulvar cancer including published and accruing Groningen International Study on Sentinel Nodes in Vulvar Cancer (GROINSS) trials and other sentinel trials from the Gynecologic Oncology Group (GOG). Here we will also review the literature on the management of recurrent vulvar cancer, highlighting current treatment options and ongoing clinical trials. The following is a report of the journal club presentation.
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The population of survivors of gynecologic malignancies continues to grow. The population of gynecologic oncology survivors has a high prevalence of pelvic floor disorders. Gynecologic oncology patients identify several survivorship needs, including a need for more focused pelvic floor disorder sequelae care. The increasing focus on patient needs following cancer treatment has led to the development of survivorship care plans and other strategies for addressing post-treatment transitions and sequelae. Common themes in patient survivorship care are patient needs for flexible and integrated care, and it is unclear if survivorship care plans in their current state improve patient outcomes. Patient referrals, specifically to urogynecologists, may help address the gaps in survivorship care of pelvic floor dysfunction.The objective of this review is to discuss the burden of pelvic floor disorders in the gynecologic population and to contextualize these needs within broader survivorship needs. The review will then discuss current strategies of survivorship care, including a discussion of whether these methods meet survivorship pelvic floor disorder needs. This review addresses several gaps in the literature by contextualizing pelvic floor disorder needs within other survivorship needs and providing a critical discussion of current survivorship care strategies with a focus on pelvic floor disorders.
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OBJECTIVE: We sought to assess the impact of antibiotic (ABX) and proton-pump inhibitor (PPI) use on progression-free (PFS) and overall survival (OS) in patients treated with adjuvant platinum-based chemotherapy (PC) for endometrial cancer (EC). METHODS: A retrospective, single-institution cohort study of EC patients treated with ≥four cycles of adjuvant PC following surgical staging from 2014 to 2020. Demographics and clinicopathologic features, including ABX and PPI use, were compared using χ2 and Fisher's exact tests. Univariate and multivariable analyses were performed, and survival outcomes were compared using the log-rank test. RESULTS: Of 325 patients, 95 (29%) received ABX, and 80 (24.6%) received PPI. ABX were associated with decreased 3-year PFS (49.9% vs. 66%; p = 0.0237) but not 3-year OS (68.9% vs. 79.9%; p = 0.0649). ABX targeting gram-positive bacteria were associated with decreased 3-year PFS (21.2% vs. 66.0% vs. 55.4%; p = 0.0038) and 3-year OS (36.5% vs. 79.9% vs. 75.6%; p = 0.0014) compared to no ABX and other ABX, respectively. PPI use was associated with decreased 3-year PFS (46.9% vs. 66.0%; p = 0.0001) and 3-year OS (60.7% vs. 81.9%; p = 0.0041) compared to no PPI. On multivariable regression analysis controlling for confounders including stage, histology, grade, radiation, and co-morbidities, PPI use was independently associated with worse PFS (HR 1.96, 95% CI 1.25-3.08; p = 0.0041) and OS (HR 2.06, 95% CI 1.01-4.18, p = 0.04). CONCLUSION: In this retrospective cohort study, we demonstrate that PPI use is independently associated with worse PFS and OS in patients with EC treated with PC. ABX use was associated with worse PFS on univariate analysis only. There is an unmet need to understand how PPI, ABX, and, potentially, the microbiome impact the effectiveness of chemotherapy in EC patients.
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Neoplasias Endometriales , Inhibidores de la Bomba de Protones , Femenino , Humanos , Estudios Retrospectivos , Inhibidores de la Bomba de Protones/uso terapéutico , Estudios de Cohortes , Platino (Metal)/uso terapéutico , Antibacterianos/uso terapéutico , Estadificación de Neoplasias , Quimioterapia Adyuvante , Neoplasias Endometriales/patologíaRESUMEN
OBJECTIVE: To determine the prevalence of Type 2 diabetes mellitus (T2DM) diagnoses during the peri-operative and survivorship periods in patients following surgical management of endometrial cancer (EC). METHODS: An IRB-approved, retrospective single-institution cohort study was performed in patients who underwent surgical management of EC from 2014 to 2020. The perioperative period was defined as the 30 days before and after surgery. T2DM diagnoses occurring during survivorship were recorded. T2DM diagnoses were defined by a HgbA1c ≥6.5% or a random blood glucose ≥200 mg/dL. Sequelae of peri-operative T2DM and predictors of future T2DM were examined utilizing univariate analysis. RESULTS: Of 519 patients meeting inclusion criteria, 37 (7.1%) were diagnosed with T2DM in the perioperative period. Patients diagnosed with T2DM in the perioperative period had significantly higher BMI (p = 0.006) compared to no T2DM, but there were no significant differences in age (p = 0.20), ethnicity/race (p > 0.05) or ECOG score (p = 0.19). The rates of intraoperative complications between groups did not significantly differ, except for vascular complications (p = 0.005), and the incidence of any postoperative complication was higher in the perioperative T2DM group (p = 0.01). With a median follow-up of 29 months [range 11.6-49.0 months], an additional 18.3% (n = 88) of the cohort met diagnostic criteria for T2DM. BMI (p < 0.001), perioperative glucose (p < 0.001), and HgbA1c (p = 0.002) demonstrate risk for a T2DM diagnosis during survivorship. CONCLUSION(S): In this retrospective cohort of EC patients, 25.4% were diagnosed with T2DM, with the majority diagnosed in the survivorship period. Surgical management and subsequent surveillance of EC presents an opportunity to diagnose at-risk patients with T2DM.
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Objective: To determine the safety and feasibility of same-day discharge (SDD) following minimally invasive hysterectomy (MIH) for elderly patients and to evaluate associations between age, frailty, and postoperative outcomes. Methods: Retrospective review was conducted of patients aged ≥ 70 who underwent MIH within a single gynecologic oncology institution from 2018 to 2020. Demographics, peri-operative factors, postoperative complications, and 30-day readmission rates were collected. Frailty was determined by an 11-point modified frailty index ≥ 2. Outcomes were compared between SDD and observation groups using Fisher's exact and Wilcoxon rank-sum tests. Results: Of 169 patients included in the analysis, 8.9% (n = 15) underwent SDD, and 91.1% (n = 154) were admitted for OBS following MIH. Demographics, peri-operative factors, and frailty rates (33% SDD vs 43.5% observation; p = 0.59) were similar between groups. 86.7% (n = 13) of SDD cases were completed before 12PM, and none were completed after 6PM. No SDD patients had early post-operative complications or hospital readmissions. Early postoperative complications were diagnosed in 9 (5.8%) patients admitted for OBS, and the 30-day hospital readmission rate for patients who underwent OBS was 8.4% (n = 13). While elderly patients who met objective frailty criteria (n = 72) did not have a higher likelihood of early post-operative complications (44.4% vs 55.6%; p = 0.909), they did have a higher likelihood of ED visit within 30 days of discharge (15.3 vs 3.1%; p = 0.009), and a trend was noted toward a higher rate of 30-day hospital readmission (12.5% vs 4.1%; p = 0.080). Conclusions: Elderly patients undergoing SDD following MIH did not have increased morbidity or mortality. Elderly patients who meet objective criteria for frailty, however, represent a more vulnerable population.
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Patients with gynecologic cancers are at risk for malnutrition, cancer cachexia, and sarcopenia. Accumulating data supports that malnourished patients with gynecologic cancer have worse overall survival, increased healthcare utilization and costs, and a higher incidence of postoperative complications and treatment toxicity than those who are not malnourished. Malnutrition is defined as insufficient energy intake, leading to altered body composition and subsequent impaired physical and cognitive function, and can result in sarcopenia and cachexia, defined as the loss of lean body mass and loss of body weight respectively. The etiology of cancer-related malnutrition is complex, resulting from a systemic pro-inflammatory state of malignancy with upregulation of muscle degradation pathways and metabolic derangements, including lipolysis and proteolysis, that may not respond to nutritional repletion alone. Numerous validated scoring systems and radiographic measures have been described to define and quantify the severity of malnutrition and muscle loss in both clinical and research settings. "Prehabilitation" and optimization of nutrition and functional status early in therapy may combat the development or worsening of malnutrition and associated syndromes and ultimately improve oncologic outcomes, but limited data exist in the context of gynecologic cancer. Multi-modality nutrition and physical activity interventions have been proposed to combat the biophysical losses related to malnutrition. Several trials are underway in gynecologic oncology patients to address these aims, but significant gaps in knowledge persist. Pharmacologic interventions and potential immune targets for combating cachexia related to malignancy are discussed in this review and may provide opportunities to target disease and cachexia. This article reviews currently available data regarding the implications, diagnostics, physiology, and intervention strategies for gynecologic oncology patients with malnutrition and its associated conditions.
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Neoplasias de los Genitales Femeninos , Desnutrición , Neoplasias , Sarcopenia , Humanos , Femenino , Caquexia/etiología , Caquexia/terapia , Caquexia/epidemiología , Sarcopenia/etiología , Sarcopenia/terapia , Neoplasias de los Genitales Femeninos/complicaciones , Neoplasias de los Genitales Femeninos/terapia , Desnutrición/complicaciones , Desnutrición/terapia , Estado NutricionalRESUMEN
OBJECTIVE: To investigate themes, quality, and reliability of gynecologic cancer-related content on the social media application TikTok. METHODS: TikTok was systematically searched for the 100 most popular posts for ovarian cancer (OC), endometrial cancer (EC), cervical cancer (CC), vulvar cancer (VC), and gestational trophoblastic disease (GTD) in August 2022. Data was collected for demographics, tone, and themes. Educational videos were rated for quality and reliability utilizing the modified DISCERN scale. Relationships between content demographics, disease sites, and themes were assessed. RESULTS: As of August 2022, the top five hashtags for each gynecologic cancer on TikTok had 466.7 million views. 430 of the top 500 posts were eligible for inclusion (OC: n = 86, CC: n = 93, EC: n = 98, GTD: n = 63, VC: n = 90). The majority of creators (n = 323, 75.1%) were White, 33 (7.7%) were Black, 20 (4.6%) were Asian/Pacific Islander (API), 10 (2.3%) were South Asian, 20 (4.7%) were Hispanic/Latino/a, 24 (5.5%) were unable to determine. Eleven central themes were identified, with significant differences when analyzed by disease site and race. The median DISCERN score for all posts was 1.0, indicating poor educational quality and reliability. When compared by race, South Asian/API posters received the highest scores (3, IQR 2.5) versus Black (2: IQR 3), Hispanic/Latino/a (2: IQR 0), and White posters (1, IQR 2) (p = 0.0013). CONCLUSION(S): Gynecologic cancer-related content on TikTok is of poor educational quality, and racial disparities in gynecologic cancer extend to social media. Opportunities exist to create more diverse content to support racial and cultural experiences in gynecologic cancer treatment.
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Neoplasias Endometriales , Neoplasias de los Genitales Femeninos , Enfermedad Trofoblástica Gestacional , Neoplasias Ováricas , Medios de Comunicación Sociales , Neoplasias del Cuello Uterino , Neoplasias de la Vulva , Femenino , Humanos , Embarazo , Escolaridad , Neoplasias de los Genitales Femeninos/terapia , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVES: To describe stage, treatment patterns, and survival for glassy cell carcinoma of the cervix (GCCC), a poorly understood rare tumor. METHODS: Clinical data and survival were compared between GCCC and more common histologic types using the National Cancer Database (NCDB) from 2004 to 2017. A retrospective review of GCCC cases at our institution from 2012 to 2020 was simultaneously performed with staging updated according to 2018 FIGO staging. Descriptive statistics and survival analyses were performed, and outcomes compared to historical references. RESULTS: 143/89,001 (0.16%) NCDB cervical cancer cases were GCCC. Compared to other histologies, GCCC cases were younger, with 74.8% diagnosed before age 50. Stage distribution was similar. Stage I cases were less commonly treated with surgery alone (19/69, 27%). 79.4% of locally advanced (stage II-IVA) cases were treated with definitive chemoradiation. GCCC demonstrated worse OS for early-stage and locally-advanced disease. No survival differences were observed for patients with stage IVB disease. Our institutional review identified 14 GCCC cases. Median age at diagnosis was 34 years. All nine early-stage cases underwent radical hysterectomy. Adjuvant radiation was given for cases meeting Sedlis criteria (4/9, 44%). All five advanced stage cases were stage IIIC and received definitive chemoradiation. Recurrence rate was 0% (0/9) for early-stage and 60% (3/5) for advanced-stage cases. 3-year PFS was 100% for early-stage and 40% for advanced-stage. 3-year OS was 100% for early-stage and 60% for advanced-stage GCCC. CONCLUSIONS: GCCC presents at earlier ages than other cervical cancer histologic types. Although NCDB showed worse OS, our more contemporary institutional review, which incorporates updated staging and newer treatment modalities found outcomes more similar to historical references of more common histologic subtypes.
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Neoplasias del Cuello Uterino , Femenino , Humanos , Adulto , Persona de Mediana Edad , Neoplasias del Cuello Uterino/patología , Estadificación de Neoplasias , Cuello del Útero/patología , Terapia Combinada , Estudios Retrospectivos , HisterectomíaRESUMEN
Gastritis related to immunotherapy use is a less commonly reported adverse effect. With increasing use of immunotherapy agents in the management of patients with endometrial cancer, even rare adverse effects are being seen more frequently in gynecologic oncology practice. A 66-year-old with recurrent mismatch repair deficient endometrial cancer was treated with single-agent pembrolizumab. She initially appeared to tolerate treatment well; however after 16 months of therapy she began to develop nausea, vomiting, and abdominal pain that resulted in 30-pound weight loss. Pembrolizumab was held out of concern for immunotherapy related toxicity. She underwent evaluation with gastroenterology including esophagogastroduodenoscopy (EGD) with biopsy that demonstrated severe lymphocytic gastritis. She was treated with IV methylprednisolone with improvement in symptoms over three days. She was then transitioned to oral prednisone at 60 mg daily with weekly taper by 10 mg, with a proton pump inhibitor (PPI) and carafate until resolution of symptoms. She subsequently had a follow up EGD with biopsy, which demonstrated resolving gastritis. She is presently doing well off of steroids with stable disease noted on her last scan after cessation of pembrolizumab.
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Objective: Gynecologic cancers are associated with a high risk of venous thromboembolism (VTE). The Khorana score is a validated tool to assess risk of VTE in cancer patients. The purpose of this study is to determine if the Khorana score can be used as a risk stratification tool for VTE in patients with uterine cancer undergoing chemotherapy. Methods: A retrospective cohort study of patients with newly diagnosed uterine cancer receiving chemotherapy over a 4-year period was conducted. The patients were stratified based on their Khorana score as well as their chemotherapy sequence, neoadjuvant or definitive versus adjuvant. Results: A total of 276 patients were included: 40 received neoadjuvant or definitive, 236 adjuvant chemotherapy. Most patients had advanced stage disease (64.5%). 18 (6.5%) patients developed VTE within 180 days of initiating chemotherapy. High Khorana score was associated with a non-significant increase in VTE (K ≥ 2 OR 1.17, CI 0.40-3.39, K ≥ 3 OR 1.69, CI 0.61-4.69) but had poor predictive accuracy based on area under the curve (K ≥ 2 0.51, K ≥ 3 0.55). The VTE rate was higher in the neoadjuvant/definitive chemotherapy group to adjuvant (12.5% vs 5.5%, p = 0.11). While the former group had a higher average Khorana score (2.35 vs 1.93, p = 0.0048), this was not predictive of VTE. Conclusions: While validated in other cancer types, the Khorana score was found to be a poor predictor of VTE in patients with uterine cancer. The use of the Khorana score to guide routine thromboprophylaxis in these patients should be used with caution and further investigation is warranted.
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High-grade serous carcinoma (HGSC) is the most common and lethal ovarian cancer subtype. PARP inhibitors (PARPi) have become the mainstay of HGSC-targeted therapy, given that these tumors are driven by a high degree of genomic instability (GI) and homologous recombination (HR) defects. Nonetheless, approximately 30% of patients initially respond to treatment, ultimately relapsing with resistant disease. Thus, despite recent advances in drug development and an increased understanding of genetic alterations driving HGSC progression, mortality has not declined, highlighting the need for novel therapies. Using a small-molecule activator of protein phosphatase 2A (PP2A; SMAP-061), we investigated the mechanism by which PP2A stabilization induces apoptosis in patient-derived HGSC cells and xenograft (PDX) models alone or in combination with PARPi. We uncovered that PP2A genes essential for cellular transformation (B56α, B56γ, and PR72) and basal phosphatase activity (PP2A-A and -C) are heterozygously lost in the majority of HGSC. Moreover, loss of these PP2A genes correlates with worse overall patient survival. We show that SMAP-061-induced stabilization of PP2A inhibits the HR output by targeting RAD51, leading to chronic accumulation of DNA damage and ultimately apoptosis. Furthermore, combination of SMAP-061 and PARPi leads to enhanced apoptosis in both HR-proficient and HR-deficient HGSC cells and PDX models. Our studies identify PP2A as a novel regulator of HR and indicate PP2A modulators as a therapeutic therapy for HGSC. In summary, our findings further emphasize the potential of PP2A modulators to overcome PARPi insensitivity, given that targeting RAD51 presents benefits in overcoming PARPi resistance driven by BRCA1/2 mutation reversions.
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Proteína BRCA1 , Neoplasias Ováricas , Femenino , Humanos , Proteína BRCA1/genética , Proteína Fosfatasa 2/genética , Proteína BRCA2/genética , Daño del ADN , Neoplasias Ováricas/tratamiento farmacológico , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Recombinación Homóloga , Muerte CelularRESUMEN
Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.
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Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Carcinosarcoma , Neoplasias Endometriales , Neoplasias Uterinas , Femenino , Humanos , Carcinoma Endometrioide/patología , Carcinosarcoma/diagnóstico , Carcinosarcoma/terapia , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Neoplasias Uterinas/patologíaRESUMEN
OBJECTIVES: To determine whether morbid obesity should serve as an independent factor in the decision for same day discharge following minimally invasive hysterectomy. METHODS: Retrospective review was performed of patients with BMI ≥ 40 who underwent minimally invasive hysterectomy within a single comprehensive cancer center between January 2018 - August 2020. Demographics, perioperative factors, post-operative monitoring, complications, and readmissions were compared between patients who underwent same day discharge and overnight observation using Fisher's exact tests and Wilcoxon rank-sum tests. RESULTS: 374 patients with BMI ≥ 40 were included. Eighty-three (22.2%) patients underwent same day discharge, and 291 (77.8%) patients underwent overnight observation. Factors associated with increased likelihood of same day discharge included younger age (median age 53 vs 58; p = 0.001), lower BMI (median BMI 45 vs 47; p = 0.005), and fewer medical co-morbidities (Charlson Co-Morbidity Index 2 vs 3; p < 0.001). On multivariate regression analysis, frailty (OR 2.16 [1.14-4.11], p = 0.019) and surgical completion time after 12 PM (OR 3.67 [2.16-6.24], p < 0.001) were associated with increased risk of overnight observation. Few patients admitted for routine overnight observation required medical intervention (n = 14, 4.8%); most of these patients were frail (64.3%). The overall hospital readmission rate within 30 days of discharge was 3.2% (n = 12), with no patients discharged on the day of surgery being readmitted. CONCLUSIONS: Morbid obesity alone should not serve as a contraindication to same day discharge following minimally invasive hysterectomy. Admission for observation was associated with low rates of clinically meaningful intervention, and patients who underwent same day discharge were not at increased risk of adverse outcome.