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1.
Mol Cancer ; 23(1): 121, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853277

RESUMO

BACKGROUND: Platinum resistance is the primary cause of poor survival in ovarian cancer (OC) patients. Targeted therapies and biomarkers of chemoresistance are critical for the treatment of OC patients. Our previous studies identified cell surface CD55, a member of the complement regulatory proteins, drives chemoresistance and maintenance of cancer stem cells (CSCs). CSCs are implicated in tumor recurrence and metastasis in multiple cancers. METHODS: Protein localization assays including immunofluorescence and subcellular fractionation were used to identify CD55 at the cell surface and nucleus of cancer cells. Protein half-life determinations were used to compare cell surface and nuclear CD55 stability. CD55 deletion mutants were generated and introduced into cancer cells to identify the nuclear trafficking code, cisplatin sensitivity, and stem cell frequency that were assayed using in vitro and in vivo models. Detection of CD55 binding proteins was analyzed by immunoprecipitation followed by mass spectrometry. Target pathways activated by CD55 were identified by RNA sequencing. RESULTS: CD55 localizes to the nucleus of a subset of OC specimens, ascites from chemoresistant patients, and enriched in chemoresistant OC cells. We determined that nuclear CD55 is glycosylated and derived from the cell surface pool of CD55. Nuclear localization is driven by a trafficking code containing the serine/threonine (S/T) domain of CD55. Nuclear CD55 is necessary for cisplatin resistance, stemness, and cell proliferation in OC cells. CD55 S/T domain is necessary for nuclear entry and inducing chemoresistance to cisplatin in both in vitro and in vivo models. Deletion of the CD55 S/T domain is sufficient to sensitize chemoresistant OC cells to cisplatin. In the nucleus, CD55 binds and attenuates the epigenetic regulator and tumor suppressor ZMYND8 with a parallel increase in H3K27 trimethylation and members of the Polycomb Repressive Complex 2. CONCLUSIONS: For the first time, we show CD55 localizes to the nucleus in OC and promotes CSC and chemoresistance. Our studies identify a therapeutic mechanism for treating platinum resistant ovarian cancer by blocking CD55 nuclear entry.


Assuntos
Antígenos CD55 , Núcleo Celular , Cromatina , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Histonas , Células-Tronco Neoplásicas , Neoplasias Ovarianas , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , Feminino , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Animais , Camundongos , Antígenos CD55/metabolismo , Antígenos CD55/genética , Linhagem Celular Tumoral , Histonas/metabolismo , Núcleo Celular/metabolismo , Cromatina/metabolismo , Metilação , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Transporte Proteico
2.
Gynecol Oncol ; 186: 161-169, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38691986

RESUMO

OBJECTIVE(S): To evaluate whether extended dosing of antibiotics (ABX) after cytoreductive surgery (CRS) with large bowel resection for advanced ovarian cancer is associated with reduced incidence of surgical site infection (SSI) compared to standard intra-operative dosing and evaluate predictors of SSI. METHODS: A retrospective single-institution cohort study was performed in patients with stage III/IV ovarian cancer who underwent CRS from 2009 to 2017. Patients were divided into two cohorts: 1) standard intra-operative dosing ABX and 2) extended post-operative ABX. All ABX dosing was at the surgeon's discretion. The impact of antibiotic duration on SSI and other postoperative outcomes was assessed using univariate and multivariable Cox regression models. RESULTS: In total, 277 patients underwent cytoreductive surgery (CRS) with large bowel resection between 2009 and 2017. Forty-nine percent (n = 137) received standard intra-operative ABX and 50.5% (n = 140) received extended post-operative ABX. Rectosigmoid resection was the most common large bowel resection in the standard ABX (89.9%, n = 124) and extended ABX groups (90.0%, n = 126), respectively. No significant differences existed between age, BMI, hereditary predisposition, or medical comorbidities (p > 0.05). No difference was appreciated in the development of superficial incisional SSI between the standard ABX and extended ABX cohorts (10.9% vs. 12.9%, p = 0.62). Of patients who underwent a transverse colectomy, a larger percentage of patients developed a superficial SSI versus no SSI (21% vs. 6%, p = 0.004). CONCLUSION(S): In this retrospective study of patients with advanced ovarian cancer undergoing CRS with LBR, extended post-operative ABX was not associated with reduced SSI, and prolonged administration of antibiotics should be avoided unless clinically indicated.


Assuntos
Antibacterianos , Procedimentos Cirúrgicos de Citorredução , Neoplasias Ovarianas , Infecção da Ferida Cirúrgica , Humanos , Feminino , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Neoplasias Ovarianas/cirurgia , Antibacterianos/administração & dosagem , Idoso , Antibioticoprofilaxia/métodos , Estudos de Coortes , Adulto
3.
J Natl Compr Canc Netw ; 22(8): 512-519, 2024 10.
Artigo em Inglês | MEDLINE | ID: mdl-39413835

RESUMO

The NCCN Guidelines for Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer provide multidisciplinary diagnostic workup, staging, and treatment recommendations for this disease. These NCCN Guidelines Insights detail how the evolution of the use of PARP inhibitors as maintenance and single-agent regimens for the treatment of ovarian cancer informed panel recommendations in the guidelines.


Assuntos
Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Neoplasias Peritoneais , Humanos , Feminino , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/terapia , Neoplasias Peritoneais/diagnóstico , Neoplasias das Tubas Uterinas/diagnóstico , Neoplasias das Tubas Uterinas/terapia , Neoplasias das Tubas Uterinas/patologia , Oncologia/normas , Oncologia/métodos , Estadiamento de Neoplasias , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
4.
Int J Gynecol Cancer ; 34(8): 1246-1252, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39002980

RESUMO

OBJECTIVE: Ovarian cancer is associated with a high rate of venous thromboembolism. Our objective is to report the incidence of venous thromboembolism in recurrent ovarian cancer, assess the impact on morbidity and mortality, and evaluate predictors of venous thromboembolism. METHODS: A retrospective single institution cohort study was performed. Patients with a diagnosis of recurrent ovarian cancer between 2007 and 2020 and no previous history of venous thromboembolism were identified. Demographic and clinical variables were collected. Univariate and multivariable analyses were performed to identify predictors of venous thromboembolism. RESULTS: Of the 345 patients included in this study, 77 (22.3%) developed a venous thromboembolism. Most (n=56, 72.7%) were actively receiving treatment at the time of diagnosis of venous thromboembolism, of whom 44 (78.6%) had received three or more lines of treatment. In total, 42 (54.5%) were admitted to hospital on diagnosis and one mortality (1.3%) occurred secondary to venous thromboembolism. An intermediate/high risk Khorana score was not predictive of venous thromboembolism (p=0.24). The risk of venous thromboembolism was significantly higher with increasing lines of chemotherapy (odds ratio 1.14, 95% confidence interval 1.02 to 1.28 per line, p=0.026). There was no significant difference in overall survival (62.9 vs 49.1 median months, p=0.29) between patients with and without venous thromboembolism. CONCLUSIONS: More than 20% of patients with recurrent ovarian cancer developed a venous thromboembolism, and most occurred after three or more lines of treatment. The risk of venous thromboembolism was higher with increasing lines of chemotherapy. While venous thromboembolism did not appear to impact survival in this population, nearly half required hospitalization, emphasizing the morbidity of venous thromboembolism and potential impact on healthcare costs. Further studies are needed to improve risk stratification for venous thromboembolism in this high risk population.


Assuntos
Neoplasias Ovarianas , Tromboembolia Venosa , Humanos , Feminino , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Estudos Retrospectivos , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/complicações , Pessoa de Meia-Idade , Incidência , Idoso , Recidiva Local de Neoplasia/epidemiologia , Adulto , Estudos de Coortes , Fatores de Risco
5.
Int J Gynecol Cancer ; 33(7): 1090-1098, 2023 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-37024239

RESUMO

OBJECTIVE: To compare response rate, progression-free survival, overall survival, and toxicity of carboplatin and gemcitabine administered on day 1 and day 8 (day1&8) versus a modified day 1-only regimen in recurrent platinum-sensitive ovarian cancer. METHODS: A retrospective single-institution cohort study was performed in women with recurrent platinum-sensitive ovarian cancer between January 2009 and December 2020 treated with carboplatin and gemcitabine on a 21-day cycle. The impact of dosing schedule on response rate, progression-free survival, overall survival, and toxicities was assessed with univariate and multivariate models. RESULTS: Of 200 patients, 26% (n=52) completed day 1&8, 21.5% (n=43) started day 1&8 but dropped day 8, and 52.5% (n=105) received day 1-only. There were no differences in demographics. Median starting carboplatin and gemcitabine doses were area under curve (AUC) 5 and 600 mg/m2 for day 1-only versus AUC4 and 750 mg/m2 among day 1&8, respectively (p<0.001). A total of 43 patients (45.3%) dropped day 8 primarily due to neutropenia (51.2%) or thrombocytopenia (30.2%). The response rates were 69.3% for day 1&8-completed, 67.5% for day 1&8-dropped, and 67.6% for day 1-only (p=0.92). Median progression-free survival was 13.1, 12.1, and 12.4 months for day 1&8-completed, day 1&8-dropped, and day 1-only, respectively (p=0.29). Median overall survival was 28.2, 33.5, and 34.3 months for the above groups (p=0.42). The rate of grade 3/4 hematologic toxicity (48.9% vs 31.4%, p=0.002), dose reductions (58.9% vs 33.7%, p<0.001), blood transfusions (22.1% vs 10.5%, p=0.025), and treatment with pegfilgrastim (64.2% vs 51%, p=0.059) were higher among day 1&8 versus day 1-only, respectively. CONCLUSIONS: There was no difference in response rate, progression-free survival, or overall survival for day 1&8 versus day 1-only, regardless of whether day 8 was dropped. Day 1&8 was associated with greater hematologic toxicity. A modified day 1-only regimen may represent an alternative to day 1&8 and warrants prospective study.


Assuntos
Gencitabina , Neoplasias Ovarianas , Humanos , Feminino , Carboplatina , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Platina/uso terapêutico , Estudos Prospectivos , Estudos Retrospectivos , Estudos de Coortes , Desoxicitidina/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico
6.
J Behav Med ; 46(1-2): 153-166, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35066696

RESUMO

Lack of trust in biomedical research, government, and health care systems, especially among racial/ethnic minorities and under-resourced communities, is a longstanding issue rooted in social injustice. The COVID-19 pandemic has further highlighted existing health and socioeconomic inequities and increased the urgency for solutions to provide access to timely, culturally, and linguistically appropriate evidence-based information about COVID-19; and ultimately to promote vaccine uptake. California's statewide alliance STOP COVID-19 CA (comprising eleven sites), leverages long standing community partnerships to better understand concerns, misinformation, and address racial/ethnic inequities in vaccine hesitancy and uptake. Using data from the California CEAL Communication Working Group, we demonstrate the wide range of strategies, communication methods, languages, and trusted messengers that have been effective in reaching diverse communities across the state. We also showcase challenges and lessons learned, such as the importance of including trusted community partners to share information or provide vaccines. These approaches, rooted in community engagement, are crucial for addressing inequities and responding to future public health emergencies.


Assuntos
COVID-19 , Hesitação Vacinal , Humanos , Pandemias , COVID-19/prevenção & controle , Grupos Raciais , California
7.
Prev Chronic Dis ; 20: E74, 2023 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-37616470

RESUMO

Taxes on sugar-sweetened beverages (SSBs), or drinks with added sugars, show promise in decreasing purchases and consumption of SSBs. Some have called for coupling such taxes with improvements in access to safe drinking water as a strategy for reducing inequities in SSB intake, yet no studies have examined such an approach. Drink Tap is a San Francisco-based program in which public tap water stations were installed in parks and public spaces (winter 2017) and promotional efforts (fall and winter 2018) encouraged water intake. At the same time, San Francisco and surrounding communities were also implementing SSB taxes. We conducted a quasi-experimental study to examine whether water access and promotion combined with SSB taxes affected beverage intake habits more than SSB taxes alone. We conducted 1-hour observations (N = 960) at 10 intervention parks (Drink Tap plus SSB taxes) and 20 comparison parks (SSB taxes only) in San Francisco Bay Area cities before (July-September 2016) and after (June-August 2019) implementation of Drink Tap. We found significant adjusted percentage increases in drinking water among visitors to intervention parks, compared with comparison parks: water from park water sources (+80%, P < .001) and water from reusable bottles (+40%, P = .02). We found no significant reductions in visitors observed drinking bottled water, juices, or SSBs. The Drink Tap intervention led to increases in water intake from park sources and reusable bottles across parks that surpassed increases achieved through SSB taxes alone. Jurisdictions should consider coupling tap water access and promotion with policies for reducing intake of SSBs.


Assuntos
Água Potável , Humanos , São Francisco , Cidades , Impostos , Paclitaxel , Abastecimento de Água
8.
Environ Monit Assess ; 195(2): 346, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36717515

RESUMO

Food waste has been considered a global problem due to its adverse impacts on food security, the environment, and the economy; hence needs urgent attention and action. Its generation is expected to increase as the world population grows rapidly, leading to more global waste. This study sought the impacts of the COVID-19 outbreak on the 1-week operation of selected casual dining restaurants in urban (Ampang, Kuala Lumpur) and suburban areas (Kota Bharu, Kelantan and Jasin, Melaka) of Peninsular Malaysia, as the local community adjusted to life with COVID-19. The food waste in this study was classified into three categories: preparation loss, serving loss, and customer's plate waste. Our material flow analysis revealed that the highest food loss at these locations came from preparation loss (51.37%), followed by serving loss (30.95%), and preparation loss (17.8%). Meanwhile, the total average electricity consumption and its carbon footprint for Ampang were 127 kWh and 13.87 kgCO2e, Kota Bharu 269.8 kWh and 29.47 kgCO2e, and Jasin 142.2 kWh and 15.54 kgCO2e, respectively. As for water, Ampang exhibited 22.93 m3 total average consumption and 7.91 kgCO2e greenhouse emissions from this source, Jasin consuming 17.11 m3 of water and releasing 5.88 kgCO2e of carbon footprint, while Kota Bharu emitted 20.21 kgCO2e of greenhouse gases from its 58.71 m3 water consumption. Our findings indicate a major 'food leak' at the preparation stage, from which the waste could be utilised as livestock feed, and that electricity consumption is a greater carbon emitter than water consumption, suggesting a need for improvement to the kitchen practices and equipment.


Assuntos
COVID-19 , Eliminação de Resíduos , Humanos , Alimentos , Restaurantes , Malásia/epidemiologia , Pandemias , COVID-19/epidemiologia , Monitoramento Ambiental , Pegada de Carbono , Água
9.
Gynecol Oncol ; 165(3): 603-609, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35410731

RESUMO

OBJECTIVE: This study aimed to explore patient-reported content on Instagram social media posts focused on gestational trophoblastic neoplasia (GTN). STUDY DESIGN: A cross-sectional search of public Instagram posts containing the term #gestationaltrophoblasticneoplasia from 1/1/2019-12/31/2019 was performed. This study included only patient-centered posts written in the English language posts. Investigators collected data for timing relative to diagnosis, subject matter, content, and tone. We utilized a staged approach to analyzing social media post content through familiarization, identifying the thematic framework, indexing, summarizing, and interpreting data. Descriptive statistical analysis was performed. RESULTS: In total, of 326 extracted posts from 1/1/2019-12/31/2019, 291 (89.3%) met the criteria for study inclusion. The majority of content was posted during chemotherapy (n = 142, 48.8%) or in the surveillance period (n = 121, 41.6%) after completion of treatment. Qualitative analysis identified ten major themes: cancer therapy and side effects (n = 142, 48.8%), pregnancy loss (n = 59, 20.3%), labs and imaging (n = 60, 20.6%), acknowledgement of a support person (n = 37, 12.7%), infertility (n = 32, 11.0%), hardships of parenting during cancer (n = 21, 7.2%), religion/spirituality (n = 18, 6.2%), diagnosis (n = 12, 4.1%) fear of recurrence (n = 10, 3.4%) and surgery (n = 7, 2.4%). Further, of the posts focused on chemotherapy side effects, approximately one-half (n = 38, 46.3%) discussed hair loss, and fatigue was reported in 25.6% (n = 21) of posts. CONCLUSIONS: In this cross-sectional study of Instagram posts using the hashtag #gestationaltrophoblasticneoplasia, we identify that women with GTN use Instagram posts to share experiences unique to their cancer diagnosis, including chemotherapy side effects, including hair loss, infertility, labs and imaging, and the hardships of parenting during cancer. This analysis provides important information regarding patient values and experiences following a diagnosis of GTN.


Assuntos
Doença Trofoblástica Gestacional , Infertilidade , Mídias Sociais , Alopecia , Estudos Transversais , Feminino , Doença Trofoblástica Gestacional/terapia , Humanos , Avaliação de Resultados da Assistência ao Paciente , Gravidez
10.
Gynecol Oncol ; 165(1): 90-96, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35272875

RESUMO

OBJECTIVE(S): To assess incidence and oncologic outcomes in women with advanced epithelial ovarian cancer (EOC) with inguinal lymph node metastasis (ILNM) at diagnosis. METHODS: An IRB-approved, retrospective single-institution cohort study was performed in women with stage III/IV EOC from 2009 to 2017. Patients with inguinal lymphadenopathy (defined as >1 cm in short axis) clinically or radiographically were identified. The impact of ILNM on progression-free survival (PFS) and overall survival (OS) were assessed. RESULTS: Of the 562 women with advanced EOC, 18 (3.2%) had ILNM at diagnosis, accounting for 25.7% of all patients with stage IVB disease (n = 70). Five patients (27.7%) had a known genetic predisposition for EOC, including BRCA1 (11.1%, n = 2), BRCA2 (11.1%, n = 2) and BRIP1 (5.6%, n = 1). The majority of patients underwent optimal primary cytoreductive surgery (CRS), including debulking of inguinal nodal metastasis (83.3%, n = 15), with 50% (n = 9) having no gross residual disease after surgery. There was no difference in PFS (19.9 vs. 19.9 vs. 17.2 months, p = 0.84) or OS (137.2 vs. 52.9 vs. 67.6 months, p = 0.29) in women with stage III/IV with ILNM, stage III/IV without ILNM, and stage IVB disease without ILNM, respectively. Progression-free survival was improved in women with ILNM who underwent an optimal resection to no macroscopic disease vs. non-optimal resection (27.4 vs. 14.3 months, p = 0.019). Median overall survival at the time of analysis did not reach statistical significance (137.2 vs. 57.3 months, p = 0.24). CONCLUSION(S): In this retrospective cohort study, 3.2% of women with advanced EOC presented with ILNM at diagnosis. Although ILNM did not portend worse clinical outcomes compared to all Stage III/IV and Stage IVB patients, respectively, resection to no gross residual disease was associated with improved PFS.


Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/patologia , Estudos de Coortes , Feminino , Humanos , Incidência , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos
11.
J Natl Compr Canc Netw ; 20(9): 972-980, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36075393

RESUMO

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias Ovarianas , Neoplasias Peritoneais , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/terapia , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estados Unidos
12.
Eur Radiol ; 32(12): 8617-8628, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35678860

RESUMO

OBJECTIVES: In the Cancer Core Europe Consortium (CCE), standardized biomarkers are required for therapy monitoring oncologic multicenter clinical trials. Multiparametric functional MRI and particularly diffusion-weighted MRI offer evident advantages for noninvasive characterization of tumor viability compared to CT and RECIST. A quantification of the inter- and intraindividual variation occurring in this setting using different hardware is missing. In this study, the MRI protocol including DWI was standardized and the residual variability of measurement parameters quantified. METHODS: Phantom and volunteer measurements (single-shot T2w and DW-EPI) were performed at the seven CCE sites using the MR hardware produced by three different vendors. Repeated measurements were performed at the sites and across the sites including a traveling volunteer, comparing qualitative and quantitative ROI-based results including an explorative radiomics analysis. RESULTS: For DWI/ADC phantom measurements using a central post-processing algorithm, the maximum deviation could be decreased to 2%. However, there is no significant difference compared to a decentralized ADC value calculation at the respective MRI devices. In volunteers, the measurement variation in 2 repeated scans did not exceed 11% for ADC and is below 20% for single-shot T2w in systematic liver ROIs. The measurement variation between sites amounted to 20% for ADC and < 25% for single-shot T2w. Explorative radiomics classification experiments yield better results for ADC than for single-shot T2w. CONCLUSION: Harmonization of MR acquisition and post-processing parameters results in acceptable standard deviations for MR/DW imaging. MRI could be the tool in oncologic multicenter trials to overcome the limitations of RECIST-based response evaluation. KEY POINTS: • Harmonizing acquisition parameters and post-processing homogenization, standardized protocols result in acceptable standard deviations for multicenter MR-DWI studies. • Total measurement variation does not to exceed 11% for ADC in repeated measurements in repeated MR acquisitions, and below 20% for an identical volunteer travelling between sites. • Radiomic classification experiments were able to identify stable features allowing for reliable discrimination of different physiological tissue samples, even when using heterogeneous imaging data.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Imagens de Fantasmas , Neoplasias/diagnóstico por imagem , Europa (Continente) , Reprodutibilidade dos Testes
13.
Gynecol Oncol ; 161(1): 211-220, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33504455

RESUMO

OBJECTIVE(S): To identify whether antibiotics (ABX) impact immunotherapy (ICI) response rate (RR), progression-free survival (PFS), and overall survival (OS) in women with recurrent endometrial (EC), cervical (CC) and ovarian cancer (OC). METHODS: This retrospective cohort study included women with recurrent EC, CC, and OC treated with ICIs from 1/1/17-9/1/2020. ABX were defined as 30 days before (pABX) or concurrently (cABX) with ICI. The impact of ABX upon PFS and OS was assessed by univariate analysis and multivariable Cox regression. RESULTS: Of 101 women, 52.5% (n = 53) had recurrent EC, 21.4% (n = 22) CC and 25.7% (n = 26) OC. 56.9% (n = 58) received ABX, with 22.8% (n = 23) pABX and 46.5% (n = 47) cABX. While no difference was observed in ICI RR for any ABX vs. none (p = 0.89) and cABX vs. none (p = 0.33), pABX (n = 23) were associated with decreased RR vs. none (n = 78) (Partial Response - 8.7% vs. 30.8%; Complete Response - 4.3% vs. 9.0%; p = 0.002). On univariate analysis, pABX were associated with worsened PFS (2.9 vs. 8.9 months; HR 2.53, 95% CI 1.48-4.31, p < 0.001) and OS (9.3 vs. 19.9 months; HR 2.29, 95% CI 1.22-4.32, p = 0.01). No PFS or OS difference was noted for cABX (PFS - 9.3 vs. 6.0 months; HR 0.70, 95% CI 0.43-1.12; p = 0.14; OS - 13.4 vs. 16.3 months; HR 0.89, 95% CI 0.51-1.54; p = 0.68). On multivariable analysis, pABX were associated with significantly decreased PFS (HR 3.10, 95% CI 1.75-5.49, p < 0.001) and OS (HR 3.03, 95% CI 1.50-6.10, p = 0.002). CONCLUSIONS: In women with recurrent EC, OC, and CC receiving ICI, pABX, but not cABX, are associated with decreased RR, PFS, and OS. Further investigation is warranted to understand predictors of ICI response in women with gynecologic cancer.


Assuntos
Antibacterianos/administração & dosagem , Neoplasias dos Genitais Femininos/tratamento farmacológico , Inibidores de Checkpoint Imunológico/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Antibacterianos/efeitos adversos , Estudos de Coortes , Interações Medicamentosas , Feminino , Neoplasias dos Genitais Femininos/imunologia , Neoplasias dos Genitais Femininos/patologia , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida
14.
Gynecol Oncol ; 163(3): 511-516, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34607712

RESUMO

OBJECTIVE: To develop and validate a comprehensive overall survival (OS) risk-scoring model in women with endometrioid endometrial cancer (EC). METHODS: Patients with EC diagnosed from 2004 to 2013 were identified through the National Cancer Database (NCDB). Patients with known lymphovascular space invasion (LVSI) status who were treated surgically (with or without adjuvant therapy) were included. Cox proportional hazards analysis was used to identify prognostic factors for OS. This model was used to assign points based on hazard ratios for risk factors and a risk score was obtained. Recursive partitioning analysis (RPA) was used to categorize patients into risk groups. Results were internally validated in a cohort of patients from our institution (CCF cohort). Risk scores were calculated and assessed in a Cox regression model, and Harrell's c-index was calculated to assess model fit. RESULTS: Among 349,404 women with EEC during the study period, 42,107 fulfilled inclusion criteria. Factors associated with worse OS were age ≥ 60, African American race, Charlson-Deyo score 1 or 2+, higher grade, LVSI, tumor size ≥2 cm, and no lymphadenectomy performed. Six risk groups were identified (scores 0-30) and OS estimated for each risk group. Risk score per 1-point increase in HR were comparable between NCDB and CCF cohorts (HR 1.21 (1.20-1.22 p < 0.001 vs 1.18 (1.12-1.25), p < 0.001), and c-index 0.80 (0.79-0.81) vs. 0.77 (0.68-0.86). Similar analysis was done in stage IA and IB. Adjuvant therapy had a beneficial effect on survival in the majority of stage IB patients, but only one of the six risk groups in stage IA EC. CONCLUSIONS: We report a comprehensive validated OS risk-scoring model for patients with.


Assuntos
Carcinoma Endometrioide/diagnóstico , Neoplasias do Endométrio/diagnóstico , Modelos Estatísticos , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Bases de Dados Factuais , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Reprodutibilidade dos Testes , Risco , Taxa de Sobrevida
15.
Gynecol Oncol ; 162(2): 368-374, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34083027

RESUMO

OBJECTIVE(S): To evaluate the impact of frailty on postoperative complications following cytoreductive surgery (CRS) with hyperthermic intra-peritoneal chemotherapy (HIPEC) in women with advanced or recurrent gynecologic cancer. METHODS: An IRB-approved single-institution prospective registry was queried for women who underwent CRS with HIPEC for advanced or recurrent gynecologic cancer from 1/1/2014-12/31/2020. Frailty was defined as a modified Frailty Index (mFI) score of ≥2. Logistic regression was used to assess the impact of mFI upon the rate of moderate or higher (≥ grade 2) Accordion postoperative complications. RESULTS: Of 141 women, 81.6% (n = 115) were non-frail with mFI of 0-1 and 18.4% (n = 26) were frail with mFI ≥2. The incidence of ≥ grade 2 complications was 21.2% (n = 14) for mFI = 0, 26.5% (n = 13) for mFI = 1, 64.7% (n = 11) for mFI = 2 and 100.0% (n = 9) for patients with mFI ≥3. The incidence of re-operation (1.7% vs. 11.5%, p = 0.044), ICU admission (13.2% vs. 34.6%, p = 0.018), acute kidney injury (6.3% vs. 30.8%, p = 0.001), and respiratory failure (0.9% vs. 19.2%, p < 0.001) were significantly lower amongst non-frail vs. frail women. On multivariable analysis, mFI ≥2 was associated with significantly increased ≥ grade 2 complications versus mFI of 0-1 (OR 9.4, 95% CI 3.3, 26.4, p < 0.001). Age (OR 1.04, 95% CI 1.00, 1.09, p = 0.07), surgical indication (recurrent vs. primary) (OR 0.71, 95% CI 0.30, 1.7, p = 0.44) and Surgical Complexity Score of Intermediate or High vs. Low (OR 1.5, 95% CI 0.67, 3.5, p = 0.31) were not associated with ≥grade 2 complications. CONCLUSIONS: Frailty, defined by the modified frailty index, is predictive of ≥grade 2 postoperative complications following CRS with HIPEC in women with gynecologic cancer. Frailty screening before CRS with HIPEC may assist patient selection and improve postoperative outcomes.


Assuntos
Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Fragilidade/diagnóstico , Neoplasias dos Genitais Femininos/terapia , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Recidiva Local de Neoplasia/terapia , Complicações Pós-Operatórias/epidemiologia , Idoso , Tomada de Decisão Clínica/métodos , Estudos de Viabilidade , Feminino , Fragilidade/etiologia , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/diagnóstico , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/diagnóstico , Estadiamento de Neoplasias , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Índice de Gravidade de Doença
16.
Gynecol Oncol ; 161(1): 194-201, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33468319

RESUMO

OBJECTIVES: To evaluate the incidence of intra-operative metabolic and electrolyte abnormalities and subsequent impact on peri-operative outcomes in women with gynecologic cancer undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC). METHODS: An IRB-approved single institution retrospective cohort study was performed in women with gynecologic cancer who underwent CRS + HIPEC. Patient demographics, intra-operative electrolyte and metabolic values and peri-operative outcomes were recorded. To assess the association of pH and lactate upon post-operative outcomes, patients were divided in four quartiles for both variables and univariate analysis was performed. RESULTS: 100 consecutive women who underwent CRS + HIPEC from 2017 to 2020 were identified. Intra-operative blood transfusion and pressor support were required in 40% and 86%, respectively. The rate of ICU admission was 17%. Longer operative time (7.0 vs. 5.3 h, p = 0.002), increased blood loss (400.0 vs. 200.0 mL, p = 0.02) and transfusion (70.6% vs. 34.1%, p = 0.005) were associated with ICU admission. Compared to patients in the highest quartile of pH, lower median pH, (7.211 vs. 7.349, p < 0.001) was associated with increased rates of ICU admission, prolonged intubation (36.0% vs. 0.0%, p < 0.05, respectively) and any post-operative complication (72.0% vs. 28.0%, p = 0.01). Similarly, need for prolonged intubation (40% vs. 0%, p = 0.04) and VTE (13.0% vs. 0%, p = 0.01) were increased in women with the highest quartile of lactate levels compared to the lowest (4.7 vs 1.9, p < 0.001). CONCLUSIONS: Intra-operative acidosis is associated with higher incidence of ICU admission and peri-operative complications following CRS + HIPEC in women with gynecologic cancer. These data support the importance of adequate intra-operative resuscitation and timely correction of hemodynamic and metabolic abnormalities.


Assuntos
Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias dos Genitais Femininos/terapia , Quimioterapia Intraperitoneal Hipertérmica/métodos , Acidose/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cisplatino/administração & dosagem , Estudos de Coortes , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Doxorrubicina/administração & dosagem , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Paclitaxel/administração & dosagem , Período Perioperatório , Estudos Retrospectivos
17.
Anticancer Drugs ; 32(10): 1086-1092, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34520432

RESUMO

To determine the effect of poly-adenosine ribose phosphatase inhibitors (PARPi) on the response to subsequent platinum-based chemotherapy (PBC) in patients with recurrent, platinum-sensitive BRCA-mutated epithelial ovarian, peritoneal, or fallopian cancer (BRCAm EOC). This is a retrospective, single-institution cohort study of patients with BRCAm EOC who received retreatment with PBC. The PFS of patients with BRCAm EOC to 2nd or 3rd PBC with and without a prior PARPi was determined. Additionally, we compared the PFS to subsequent PBC following a prior PARPi for BRCAm and non-BRCAm. One hundred and fifteen patients with BRCAm EOC received a 2nd PBC and 55 received a 3rd PBC. The median PFS was 2.3 and 2.4 times longer, respectively for patients who did not receive a PARPi, (2nd P = 0.005, 3rd P < 0.001). Among 20 PARPi exposed patients with BRCAm EOC the PFS to a 2nd or 3rd PBC was worse at 8.0 months vs. 19.1 months HR 4.01 [2.25,7.16], P < 0.001. Following PARPi exposure the PFS for patients with BRCAm EOC was similar for patients with platinum-free intervals of 6-12, 12-24 and >24 months. Following PARPi exposure the PFS was similar for patients with BRCAm EOC and non BRCAm EOC. Among patients with BRCAm EOC PARPi exposure significantly reduced PFS following 2nd and 3rd PBC. PARPi exposure nullifies established prognostic factors (i.e. platinum-free interval and BRCA mutational status) in platinum-sensitive recurrent ovarian cancer.


Assuntos
Proteína BRCA2/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Neoplasias Ovarianas/patologia , Compostos de Platina/uso terapêutico , Intervalo Livre de Progressão , Estudos Retrospectivos
18.
J Natl Compr Canc Netw ; 19(2): 191-226, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33545690

RESUMO

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.


Assuntos
Carcinoma Epitelial do Ovário , Neoplasias Ovarianas , Adenocarcinoma de Células Claras , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/terapia , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/terapia
19.
Curr Oncol Rep ; 23(8): 92, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34125319

RESUMO

PURPOSE OF REVIEW: We review the emerging evidence regarding the relationship between the microbiota of the gastrointestinal and female reproductive tracts and gynecologic cancer. RECENT FINDINGS: The microbiome has essential roles in maintaining health. In recent years, the microbiota of the gastrointestinal and female reproductive tracts have been linked to many diseases, including gynecologic cancer. Alterations to the bacterial populations in a microbiota, or dysbiosis, have been shown to favor a pro-carcinogenic state through altered immune responses, dysregulated hormone metabolism, and modulation of the cell cycle. Pre-clinical and clinical studies have emerged, demonstrating that specific bacteria or microbial communities may be associated with increased risk for uterine, ovarian, and cervical cancers. Notably, numerous studies have linked a non-Lactobacillus-dominant vaginal microbiota, composed of anaerobic bacteria, with HPV infection, persistence, and development of invasive cervical cancer. Similarly, next-generation high-throughput sequencing techniques have enabled the characterization of unique microbiotas in patients with malignant and benign gynecologic conditions, shedding light on new associations between bacterial species and gynecologic cancers. Harnessing the power of the microbiome for early diagnosis, therapeutic intervention and modulation creates tremendous potential to optimize gynecologic cancer outcomes in the future.


Assuntos
Microbioma Gastrointestinal , Neoplasias dos Genitais Femininos/microbiologia , Genitália Feminina/microbiologia , Feminino , Gastroenteropatias/microbiologia , Trato Gastrointestinal/microbiologia , Neoplasias dos Genitais Femininos/metabolismo , Neoplasias dos Genitais Femininos/terapia , Genitália Feminina/metabolismo , Humanos
20.
Gynecol Oncol ; 159(3): 699-705, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32950250

RESUMO

OBJECTIVE(S): To determine whether antibiotic treatment (ABX) during platinum chemotherapy (PC) for epithelial ovarian cancer (EOC) impacts progression-free survival (PFS) and overall survival (OS). STUDY DESIGN: Retrospective single institution cohort study in women with newly diagnosed stage III/IV EOC (n = 424) who underwent cytoreductive surgery (CRS) and PC from 2009 to 2015. ABX for >48 h, including ABX against gram-positive (anti-G + ABX) bacteria were recorded. The impact of ABX on PFS and OS was assessed using univariate and multivariable Cox regression models. RESULTS: Of 424 eligible women, 34.7% (n = 147) received ABX, with 11.3% (n = 48) treated with anti-G + ABX. ABX decreased PFS (17.4 vs. 23.1 months, HR 1.50, 95% CI 1.20-1.88, p < 0.001) and OS (45.6 vs. 62.4 months, HR 1.63, 95% CI 1.27-2.08, p < 0.001) compared to no ABX. Similarly, anti-G + ABX worsened PFS (16.5 vs. 23.1 months; HR 1.85, 95% CI 1.33-2.55) and OS (35.0 vs. 62.4 months; HR 2.12, 95% CI 1.50-3.0, p < 0.001). On multivariable analysis, all ABX and anti-G + ABX significantly worsened PFS (HR 1.31, 95% CI 1.04-1.65, p = 0.02), (HR 1.50, 95% CI 1.07-2.10, p = 0.02) and OS (HR 1.52, 95% CI 1.18-1.96, p = 0.001), (HR 1.83, 95% CI 1.27-2.62, p = 0.001) respectively. Increased Clavien Dindo score was associated with worsened PFS (1-2 - HR 1.52, 95% CI 1.14-2.03, p = 0.004; 3-4 - HR 1.86, 95% CI 1.27-2.72, p = 0.001) but not OS (1/2 - HR 1.35, 95% CI 0.97-1.88, p = 0.08; 3/4 - HR 1.53, 95% CI 1.00-2.34, p = 0.05); residual disease (p < 0.05) and neoadjuvant chemotherapy (p < 0.001) were associated with worse PFS and OS. CONCLUSION(S): In this retrospective cohort study of women with advanced EOC undergoing PC, ABX treatment was associated with decreased PFS and OS. Mechanistic studies are needed to investigate the negative impact of ABX upon PC response in EOC.


Assuntos
Antibacterianos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/mortalidade , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/mortalidade , Idoso , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Quimioterapia Adjuvante , Cisplatino/uso terapêutico , Ciclofosfamida/uso terapêutico , Procedimentos Cirúrgicos de Citorredução , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/prevenção & controle , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Intervalo Livre de Progressão , Estudos Retrospectivos
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