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1.
J Pediatr Surg ; 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38614951

RESUMO

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.

2.
Gynecol Oncol ; 183: 78-84, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38554477

RESUMO

OBJECTIVE: The combination of dostarlimab with carboplatin and paclitaxel has demonstrated improved progression-free survival (PFS) and overall survival (OS) in primary advanced and recurrent endometrial cancer (EC). However, prior studies have not found immunotherapy to be cost-effective, or cost-effective only in specific subgroups, of recurrent endometrial cancer. This study aimed to determine the cost-effectiveness of combination therapy compared to chemotherapy alone. METHOD: A partitioned survival model was developed to compare the cost and effectiveness of dostarlimab in combination with chemotherapy compared to chemotherapy alone in primary advanced or recurrent endometrial cancer. Clinical data was derived from the RUBY trial and drug costs from average sale prices. The incremental cost-effectiveness ratio (ICER) was compared to a set willingness to pay (WTP) of $100,000/QALY to determine cost-effectiveness. One-way and probabilistic sensitivity analyses were performed. RESULTS: In the intention-to-treat (ITT) population, the dostarlimab combination incurred an additional cost of $308,430 but provided an additional 5.67 QALYs compared to chemotherapy alone. The ICER was $54,406/QALY. The dostarlimab combination was cost-effective compared to chemotherapy alone irrespective of MMR expression, with an ICER of $32,287/QALY for MMR deficient (MMRd) EC and $85,744/QALY for MMR proficient (MMRp) EC. Probabilistic sensitivity analysis demonstrated that the combination was cost-effective in 98.2% of iterations at the current WTP threshold. CONCLUSIONS: Despite the higher cost, adding dostarlimab to platinum chemotherapy significantly improves QALYs, rendering this regimen cost-effective relative to chemotherapy alone for treating primary advanced or recurrent EC. Combination therapy is a cost-effective approach for this patient population compared to chemotherapy alone.

3.
J Natl Compr Canc Netw ; 22(2): 117-135, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38503056

RESUMO

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.


Assuntos
Neoplasias Vulvares , Feminino , Humanos , Adenocarcinoma/patologia , Neoplasias dos Genitais Femininos , Doença de Paget Extramamária/diagnóstico , Doença de Paget Extramamária/etiologia , Doença de Paget Extramamária/terapia , Neoplasias Cutâneas , Neoplasias Vulvares/diagnóstico , Neoplasias Vulvares/epidemiologia , Neoplasias Vulvares/etiologia
4.
Gynecol Oncol ; 182: 51-56, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262238

RESUMO

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.


Assuntos
Doxorrubicina/análogos & derivados , Neoplasias Ovarianas , Humanos , Feminino , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Estudos Retrospectivos , Platina/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Polietilenoglicóis
5.
Gynecol Oncol Rep ; 50: 101310, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38093798

RESUMO

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.

6.
J Natl Compr Canc Netw ; 21(12): 1224-1233, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38081139

RESUMO

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.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Neoplasias do Colo do Útero/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
7.
Int J Gynecol Cancer ; 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37935522

RESUMO

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.

8.
Gynecol Oncol ; 178: 14-22, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37741201

RESUMO

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.


Assuntos
Neoplasias do Endométrio , Inibidores da Bomba de Prótons , Feminino , Humanos , Estudos Retrospectivos , Inibidores da Bomba de Prótons/uso terapêutico , Estudos de Coortes , Platina/uso terapêutico , Antibacterianos/uso terapêutico , Estadiamento de Neoplasias , Quimioterapia Adjuvante , Neoplasias do Endométrio/patologia
9.
Gynecol Oncol ; 177: 46-52, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37639902

RESUMO

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.

10.
Gynecol Oncol Rep ; 48: 101227, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37415961

RESUMO

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.

11.
Gynecol Oncol ; 175: 142-155, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37385068

RESUMO

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.


Assuntos
Neoplasias dos Genitais Femininos , Desnutrição , Neoplasias , Sarcopenia , Humanos , Feminino , Caquexia/etiologia , Caquexia/terapia , Caquexia/epidemiologia , Sarcopenia/etiologia , Sarcopenia/terapia , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/terapia , Desnutrição/complicações , Desnutrição/terapia , Estado Nutricional
12.
Gynecol Oncol ; 175: 81-87, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37329872

RESUMO

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.


Assuntos
Neoplasias do Endométrio , Neoplasias dos Genitais Femininos , Doença Trofoblástica Gestacional , Neoplasias Ovarianas , Mídias Sociais , Neoplasias do Colo do Útero , Neoplasias Vulvares , Feminino , Humanos , Gravidez , Escolaridade , Neoplasias dos Genitais Femininos/terapia , Reprodutibilidade dos Testes
13.
Gynecol Oncol ; 173: 15-21, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37037083

RESUMO

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.


Assuntos
Neoplasias do Colo do Útero , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/patologia , Estadiamento de Neoplasias , Colo do Útero/patologia , Terapia Combinada , Estudos Retrospectivos , Histerectomia
14.
Gynecol Oncol Rep ; 47: 101174, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37102082

RESUMO

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.

15.
Gynecol Oncol Rep ; 46: 101156, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36910448

RESUMO

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.

16.
J Natl Compr Canc Netw ; 21(2): 181-209, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36791750

RESUMO

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.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma Endometrioide , Carcinossarcoma , Neoplasias do Endométrio , Neoplasias Uterinas , Feminino , Humanos , Carcinoma Endometrioide/patologia , Carcinossarcoma/diagnóstico , Carcinossarcoma/terapia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/terapia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/terapia , Neoplasias Uterinas/patologia
17.
Mol Cancer Ther ; 22(5): 599-615, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-36788429

RESUMO

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.


Assuntos
Proteína BRCA1 , Neoplasias Ovarianas , Feminino , Humanos , Proteína BRCA1/genética , Proteína Fosfatase 2/genética , Proteína BRCA2/genética , Dano ao DNA , Neoplasias Ovarianas/tratamento farmacológico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Recombinação Homóloga , Morte Celular
18.
Gynecol Oncol ; 170: 203-209, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36709661

RESUMO

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.


Assuntos
Laparoscopia , Obesidade Mórbida , Feminino , Humanos , Pessoa de Meia-Idade , Alta do Paciente , Estudos de Viabilidade , Laparoscopia/efeitos adversos , Histerectomia/efeitos adversos , Estudos Retrospectivos , Readmissão do Paciente , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos
19.
Am J Obstet Gynecol ; 228(5): 555.e1-555.e8, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36574873

RESUMO

BACKGROUND: Uterine cancers are associated with a high risk for venous thromboembolisms. The American Society of Clinical Oncology practice guidelines recommend that all patients undergoing pelvic surgery for cancer should receive extended pharmacologic thromboprophylaxis with the duration being dependent on risk. However, risk stratification for patients with uterine cancer is not clearly defined. The Caprini score is the most widely used risk assessment model but it has been found to have limited use in the gynecologic oncology population. A modified Caprini score has been explored in other populations. The Khorana score is an additional risk assessment model that has not been studied in this context. OBJECTIVE: Our objective was to evaluate the ability of a modified Caprini model and the Khorana score to risk stratify patients with uterine cancer for postoperative venous thromboembolisms within 90 days of surgery. STUDY DESIGN: Following institutional review board approval, a retrospective cohort study was performed, and all patients with uterine cancer who underwent a hysterectomy over a 4-year period were included. The Caprini and Khorana scores were calculated for each patient. The Caprini score cutoff for highest risk was evaluated at ≥7, ≥8, and ≥9 (modified Caprini) and the Khorana score cutoff was evaluated at ≥2 and ≥3. To determine the prognostic use of each score and other clinico-pathologic criteria related to the development of a venous thromboembolism, univariate analyses were performed using independent t tests, chi-square tests, or Fisher's exact tests; a multivariate analysis was performed using logistic regression. RESULTS: A total of 954 patients were included. The rate of venous thromboembolism development was 1.7% (16/954). A minimally invasive surgical approach was used in 90.5% (863/954) of patients. The mean Caprini score for patients with a venous thromboembolism was 10.3 compared with 8.1 for patients without a venous thromboembolism (95% confidence interval, 1.17-3.33; P<.0001). The mean Khorana score for the venous thromboembolism group was 2.4 vs 1.9 for those without (95% confidence interval, 0.04-0.82; P=.03). Both the Caprini and Khorana scores were found to be associated with venous thromboembolisms, but only a Caprini score with a cutoff of ≥8 or ≥9 was statistically significant (risk ratio, 31.25; 95% confidence interval, 1.88-519.49; risk ratio, 4.59; 95% confidence interval, 1.49-14.13, respectively), with high accuracy based on the area under the curve (0.75 and 0.68, respectively). Of the minimally invasive subgroup, 11.7% (101/863) of patients had same-day discharge with no postoperative thromboprophylaxis; none of these patients developed venous thromboembolisms. Despite extended prophylaxis among the laparotomy patients (30 days), the rate of venous thromboembolisms was more than 3 times that of the minimally invasive group (5.49% vs 1.7%). Advanced tumor stage and leukocytosis were noted to be independent risk factors for venous thromboembolisms. CONCLUSION: Our study suggests that using a modified Caprini score could help to identify the highest-risk patients who would benefit from prolonged thromboprophylaxis, could reduce the incidence of postoperative venous thromboembolisms, and could minimize the cost and harm of overtreatment. These findings need to be validated in a prospective manner, and further research is needed to determine the optimal duration of therapy.


Assuntos
Neoplasias dos Genitais Femininos , Neoplasias Uterinas , Tromboembolia Venosa , Trombose Venosa , Humanos , Feminino , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Anticoagulantes , Estudos Retrospectivos , Estudos Prospectivos , Trombose Venosa/epidemiologia , Medição de Risco , Fatores de Risco , Neoplasias dos Genitais Femininos/complicações , Neoplasias Uterinas/cirurgia , Neoplasias Uterinas/complicações , Complicações Pós-Operatórias/epidemiologia
20.
Gynecol Oncol Rep ; 42: 101040, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35855965

RESUMO

Objective: To evaluate the association between pre-treatment neutrophil-to-lymphocyte ratio (NLR) and survival outcomes among patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors. Methods: A retrospective analysis of patients with recurrent/metastatic cervical cancer treated with PD-1/PD-L1 inhibitors from 2016 to 2021 was conducted. Progression free survival (PFS) and overall survival (OS) outcomes were assessed for patients stratified by NLR (<8 vs ≥ 8) utilizing Kaplan-Meier method. Univariable analysis was performed to compare baseline characteristics between the two groups. Results: A total of 49 patients were included in analysis. A majority of patients had squamous cell histology (57%), were PD-L1 positive (55%), received ≤ 1 prior lines of systemic therapy (57%), and had distant metastatic disease at the time of treatment (69%). The groups were well-balanced with respect to age, race, histology, smoking status, PD-L1 positivity, prior lines of treatment (≤1 vs > 1), prior radiation therapy, ECOG performance status, and disease distribution for patients with a NLR < 8 (n = 35) compared to those with a NLR ≥ 8 (n = 14). A pre-treatment NLR of < 8 was associated with improved survival (p < 0.01), with 57% (95% CI: 41%, 78%) probability of survival at one year compared to 26% (95% CI: 10%, 66%) for those with NLR ≥ 8. No statistically significant differences in probability of PFS at 1 year were seen between NLR < 8 compared to those with NLR ≥ 8 (p = 0.70). Conclusions: Pre-treatment NLR may hold prognostic value for patients with metastatic/recurrent cervical cancer treated with PD-1/PD-L1 inhibitors, with NLR < 8 associated with improved survival.

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