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1.
Nat Commun ; 11(1): 4995, 2020 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33020491

RESUMO

Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency of mutation in CTNNB1 (43%), PIK3CA (43%), ARID1A (36%), PTEN (29%), KRAS (26%), TP53 (26%) and SOX8 (19%), a recurrently-mutated gene previously unreported in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy is constructed, identifying clinically distinct EnOC subtypes: cases with TP53 mutation demonstrate greater genomic complexity, are commonly FIGO stage III/IV at diagnosis (48%), are frequently incompletely debulked (44%) and demonstrate inferior survival; conversely, cases with CTNNB1 mutation, which is mutually exclusive with TP53 mutation, demonstrate low genomic complexity and excellent clinical outcome, and are predominantly stage I/II at diagnosis (89%) and completely resected (87%). Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.


Assuntos
Carcinoma Endometrioide/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Variações do Número de Cópias de DNA , Feminino , Humanos , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Transdução de Sinais , Sequenciamento Completo do Exoma
2.
Yonsei Med J ; 61(11): 935-941, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33107236

RESUMO

PURPOSE: Salvage second-line chemotherapy is usually recommended for patients with advanced epithelial ovarian cancer (AEOC) who develop progressive disease (PD) after neoadjuvant chemotherapy (NAC). Herein, we investigated the role of cytoreductive surgery (CRS) for such patients. MATERIALS AND METHODS: We retrospectively reviewed the medical records of 36 patients with AEOC who developed PD after receiving NAC at two tertiary academic centers with different treatment strategies between 2001 and 2016. Patients who developed PD after NAC were consistently treated with CRS at one hospital (group A; n=13) and second-line chemotherapy at another (group B; n=23). The clinical characteristics and treatment outcomes were compared between the groups. RESULTS: Overall survival (OS) was longer in group A than in group B (19.4 months vs. 7.9 months; p=0.011). High-grade serous histology was associated with longer OS than non-high-grade serous types. In group A, optimal surgery resection (<1 cm) was achieved after CRS in 6 patients (46%). Multivariate analysis showed that the treatment option was the only independent predictive factor for OS (hazard ratio, 2.30; 95% confidence interval, 1.02-5.17; p=0.044). CONCLUSION: CRS may result in a survival benefit even in patients with AEOC who develop PD after NAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Procedimentos Cirúrgicos de Citorredução/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante/mortalidade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
3.
Nat Commun ; 11(1): 5173, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057068

RESUMO

In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.


Assuntos
Vacinas Anticâncer/administração & dosagem , Células Dendríticas/transplante , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ovarianas/terapia , Células Th17/imunologia , Idoso , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/imunologia , Intervalo Livre de Doença , Feminino , Receptor 1 de Folato/imunologia , Humanos , Imunidade Humoral , Injeções Intradérmicas , Interferon gama/metabolismo , Interleucina-17/metabolismo , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Células Th17/metabolismo , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos
4.
Medicine (Baltimore) ; 99(36): e22100, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32899091

RESUMO

Intraperitoneal (IP) chemotherapy is believed to prolong the survival of patients with advanced ovarian cancer after primary debulking surgery. However, there is little knowledge about IP chemotherapy in the setting of neoadjuvant chemotherapy, and there are contradictory conclusions about adjuvant IP chemotherapy. Here, we evaluated the feasibility of neoadjuvant and adjuvant IP chemotherapy in patients with advanced epithelial ovarian cancer (AEOC).We retrospectively reviewed the data of 114 patients with AEOC who received neoadjuvant chemotherapy followed by laparoscopic conservative interval debulking surgery (NACT + LIDS) in our institution from January 1, 2009 to December 31, 2017.The median overall survival (OS) was 56 months and the median disease-free interval (DFI) was 14 months for the entire study population. Neoadjuvant IP chemotherapy cycles were crucial for the treatment of no gross residual (R0) disease (hazard ratio [HR] = 0.446, 95% confidence interval [CI] = 0.245-0.811), which was independently associated with OS of the entire study population (HR = 9.589, 95% CI = 3.911-23.507). In addition, residual disease and body mass index (BMI) were the prognostic factors for DFI (HR = 6.022, 95% CI = 3.632-9.986; HR = 1.085, 95% CI = 1.012-1.163). However, adjuvant IP cycles along with BMI were the determining factors for DFI in the R0 group (HR = 0.703, 95% CI = 0.525-0.941; HR = 1.130, 95% CI = 1.025-1.247), and were associated with OS in the R0 group (HR = 0.488, 95% CI = 0.289-0.824). The OS and DFI Kaplan-Meier curves stratified by adjuvant IP chemothearpy cycles within the R0 group were statistically significant (P = .024 and P = .033, respectively).Our results showed improvement in patients with AEOC in terms of survival, thus suggesting the feasibility of neoadjuvant and adjuvant IP chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Índice de Massa Corporal , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Infusões Parenterais , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Estudos Retrospectivos
5.
Medicine (Baltimore) ; 99(38): e21840, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957308

RESUMO

BACKGROUND: The prognostic significance of preoperative prognostic nutritional index (PNI) in ovarian cancer (OC) is uncertain, and this study is aimed to clarify the prognostic significance. METHODS: We used 4 common databases for conducting a systematic review and meta-analysis, and eligible studies were included in the analysis. The association of preoperative PNI with overall survival (OS), progression-free survival (PFS), and clinicopathological parameters was analyzed. RESULTS: A total of 2050 patients with OC receiving the surgical treatment were analyzed in this study. Patients with low PNI tended to have a shorter OS (hazard ratio [HR] = 1.82, 95% CI = 1.30-2.55, P < .01) and PFS (HR = 1.91, 95% CI = 1.53-2.39, P < .01) compared with those with high PNI. Besides, low PNI was significantly associated with more advanced International Federation of Gynecology and Obstetrics stage (P < .01), the occurrence of ascites (P < .01), larger residual tumor (P < .01), insensitive to chemotherapy (P < .01), and higher CA125 (P < .01) compared with high PNI in OC. CONCLUSION: Low preoperative PNI is associated with shorter OS, shorter PFS, and worse clinicopathological parameters in OC. Low preoperative PNI is an unfavorable prognostic indicator of patients with OC.


Assuntos
Estado Nutricional/fisiologia , Neoplasias Ovarianas/mortalidade , Antígeno Ca-125/sangue , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Proteínas de Membrana/sangue , Prognóstico , Modelos de Riscos Proporcionais
6.
Anticancer Res ; 40(9): 5255-5261, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878814

RESUMO

BACKGROUND/AIM: Treatment of recurrent platinum-resistant ovarian cancer remains challenging due to the development of resistance to chemotherapy. Cabazitaxel is a new taxane that has demonstrated beneficial effect in prostate cancer patients resistant to docetaxel. Therefore, it could be anticipated to possibly also have an effect on chemotherapy resistant ovarian cancer. PATIENTS AND METHODS: Twenty-six patients with chemotherapy-resistant epithelial ovarian cancer, fallopian tube or peritoneal cancer were treated with cabazitaxel at a dose of 25 mg/m2 (on day 1 of each 3-week cycle), until progression or inacceptable toxicity, between September 2015 and April 2018. The fraction of patients without progression after three months of treatment was the primary endpoint. Prophylaxis with granulocyte colony-stimulating factor (G-CSF) was prescribed to all patients. RESULTS: The median number of cabazitaxel infusions was 4 (range=1-18). In general, cabazitaxel was well-tolerated. The fraction of patients alive and without progression after 3 months of treatment was 54% (14/26). The response rate was 46% (12/26) according to the Gynecological Cancer Intergroup (GCIG) criteria for CA125. Partial response (PR), evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST), was found in 4/26 patients (15%). By intention-to-treat analysis, the median progression-free survival (PFS) was 3.9 months (95% CI=1.9-4.4) using the combination of CA125 or RECIST (whichever came first), while the median overall survival (OS) was 8.4 months (95% CI=5.1-11.0). CONCLUSION: Cabazitaxel holds promise as a drug in recurrent platinum-resistant ovarian cancer. It demonstrated efficacy and in general, the toxicity was manageable.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Taxoides/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Prognóstico , Qualidade de Vida , Recidiva , Retratamento , Taxoides/administração & dosagem , Taxoides/efeitos adversos , Resultado do Tratamento
7.
Anticancer Res ; 40(9): 5285-5290, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878818

RESUMO

BACKGROUND/AIM: Chemotherapy with additional bevacizumab is the standard treatment for primary and recurrent ovarian cancer. We aimed to investigate the clinical utility and safety of bevacizumab when used in combination with chemotherapy after disease progression. PATIENTS AND METHODS: This retrospective, observational study recruited patients treated for recurrent ovarian cancer from 2014 to 2016. We evaluated the effects of bevacizumab with chemotherapy in patients whose disease had progressed following treatment with bevacizumab. We assessed progression-free survival and adverse events. RESULTS: Thirty-three patients received post-progression treatment with bevacizumab. The median progression-free survival was 8.7 months (95% confidence interval=5.5-11). The progression-free survival was compared pre- and post-progression treatment, and was longer in platinum-resistant than platinum-sensitive cases after treatment (p=0.06). The most common non-hematological toxicity was proteinuria. The incidence of serious adverse events was low. CONCLUSION: Continuous administration of bevacizumab may be beneficial for ovarian cancer patients after disease progression.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Prognóstico , Recidiva , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
8.
Niger J Clin Pract ; 23(8): 1141-1147, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32788493

RESUMO

Aims: This study was aimed at investigating the prognostic impact of pretreatment thrombocytosis in epithelial ovarian cancer (EOC) patients in Lagos, Nigeria. Methods: This was a retrospective cohort study involving the review of the clinical record of 72 patients with histologically confirmed EOC who were managed at the Lagos University Teaching Hospital, Lagos, Nigeria over a 7-year period from January 2010 to December 2016. Information on the sociodemographic data and platelet counts at diagnosis of EOC were retrieved from the patients' medical records. Descriptive statistics were then computed for all baseline patients' characteristics. Survival analyses were carried out using the Kaplan-Meier estimates. Multivariate analysis of these data was performed with the Cox proportional hazards model. Results: This study revealed that the prevalence of pretreatment thrombocytosis was 41.7% among the women with EOC. Fifty-three (73.6%) of the women had the advanced-stage disease (FIGO stage III-IV) while 52 (72.2%) had high-grade disease (II-III). The majority (66.7%) of the women had a serous histological type of EOC while 76.4% had documented recurrence. Pretreatment thrombocytosis was significantly associated with the women's parity (P = 0.009), serum carbohydrate antigen 125 levels (P = 0.018), median progression-free survival (PFS) (P < 0.001), 3-year median overall survival (OS) (P < 0.001), type of primary treatment (P = 0.002), extent of cytoreduction (P < 0.001), presence of ascites (P = 0.002), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.008), and histological type (P = 0.011). Pretreatment thrombocytosis was negatively associated with PFS (hazard ratio [HR] = 0.25; 95% CI 0.83, 0.75; P = 0.014) and 3-year OS (HR = 0.03; 95% CI 0.03, 0.27; P = 0.002). Conclusions: The study suggests that pretreatment thrombocytosis may be a useful predictor of survivals in EOC patients.


Assuntos
Transtornos Plaquetários/etiologia , Carcinoma Epitelial do Ovário/mortalidade , Neoplasias Ovarianas/mortalidade , Trombocitose/epidemiologia , Adulto , Idoso , Antígenos Glicosídicos Associados a Tumores/sangue , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Nigéria/epidemiologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/patologia , Contagem de Plaquetas , Período Pré-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Trombocitose/sangue
9.
Medicine (Baltimore) ; 99(32): e21560, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769897

RESUMO

Breast cancer and ovarian cancer are closely related. The major common risk factors of these 2 types of cancer are likely genetic factors. However, few studies have shown any common characteristics in patients who have both types of these 2 cancers. The purpose of this retrospective study is to explore the clinical characteristics and survival outcomes of patients with both primary breast cancer and primary ovarian cancer.A cohort of patients who had a history of both primary breast cancer and primary ovarian cancer were enrolled, and they received treatment in the Peking Union Medical College Hospital between January 1, 2010, and December 31, 2018. Both descriptive statistics analysis and survival analysis were performed for analysis.A total of 114 patients with both primary breast cancer and primary ovarian cancer were included in the study. The median (range) follow-up was 129.5 (20-492) months. The average interval time between the diagnosis of 2 types of cancer was 79.4 months in patients having ovarian cancer firstly and was 115.9 months in patients having breast cancer firstly. The 5- and 10-year overall survival (OS) rates were 91.5% and 81.7% for patients with ovarian cancer following breast cancer, respectively, and 90.6% and 87.5% for patients with breast cancer following ovarian cancer, respectively. Multivariate analysis revealed that independent predictors of OS were the age of diagnosis of the first tumor and the time interval between two types of tumor in patients with ovarian cancer following breast cancer.Most breast cancer or ovarian cancer occurred within 5 years after being diagnosed with the first tumor, and the interval time was significantly shorter in patients with previous ovarian cancer. The prognosis is likely positively correlated to the interval time between the occurrences of two types of cancer.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Ovarianas/mortalidade , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida , Fatores de Tempo
10.
Medicine (Baltimore) ; 99(27): e20802, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629664

RESUMO

It is imperative to further the understanding of the drug resistance mechanisms of ovarian cancer (OC) and to identify useful biological markers for prognosis prediction.Cormine, cBioportal, and The Cancer Genome Atlas databases were used to search microarray data of gene methylation related to OC, drug resistance in OC, and prognosis, and to analyze methylated genes potentially inducing the drug resistance in OC. Fifty-five DNA-methylated genes significantly associated with drug resistance in OC were screened, and the regulatory mechanisms underlying changes in methylation levels of these genes were systematically integrated.Enrichment and annotation of biological processes indicated that most of the above DNA-methylated genes were significantly associated with cell proliferation and cell cycle. In addition, pathway enrichment demonstrated that the above DNA-methylated genes were significantly associated with PI3K-AKT and P53 signaling pathways. Among the 55 genes, 4 were significantly associated with OC prognostic disease-free survival, namely bromodomain containing 4, PDZ domain containing 1 (PDZK1), phosphatase and tensin homolog, and TNF receptor superfamily member 10c; 5 were significantly related to overall survival, namely bromodomain containing 4, PDZK1, PIK3C2B, Rh associated glycoprotein, and DYRK; among them, the degree of methylation of TNF receptor superfamily member 10c, PDZK1, and Rh associated glycoprotein genes was significantly correlated with mRNA expression. Furthermore, PDZK1, Rh associated glycoprotein, and TNF receptor superfamily member 10c genes showed significant hypomethylation in drug-resistance tissues of OC, and their mRNAs had significantly high expression.The association between the methylation of these 55 genes and OC and drug resistance in OC, in addition to bioinformatics analyses clarify the important mechanisms of gene methylation in the development, progression, and drug resistance of OC.


Assuntos
Metilação de DNA/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Big Data , Proliferação de Células , Classe II de Fosfatidilinositol 3-Quinases/genética , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Neoplasias Ovarianas/mortalidade , Prognóstico , Análise Serial de Proteínas , Transdução de Sinais
11.
Nat Commun ; 11(1): 3546, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669559

RESUMO

Advanced ovarian cancer usually spreads to the omentum. However, the omental cell-derived molecular determinants modulating its progression have not been thoroughly characterized. Here, we show that circulating ITLN1 has prognostic significance in patients with advanced ovarian cancer. Further studies demonstrate that ITLN1 suppresses lactotransferrin's effect on ovarian cancer cell invasion potential and proliferation by decreasing MMP1 expression and inducing a metabolic shift in metastatic ovarian cancer cells. Additionally, ovarian cancer-bearing mice treated with ITLN1 demonstrate marked decrease in tumor growth rates. These data suggest that downregulation of mesothelial cell-derived ITLN1 in the omental tumor microenvironment facilitates ovarian cancer progression.


Assuntos
Carcinoma Epitelial do Ovário/secundário , Citocinas/metabolismo , Lectinas/metabolismo , Omento/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Animais , Carcinoma Epitelial do Ovário/sangue , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/terapia , Linhagem Celular Tumoral/transplante , Movimento Celular , Proliferação de Células , Transformação Celular Neoplásica/metabolismo , Citocinas/administração & dosagem , Citocinas/sangue , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Proteínas Ligadas por GPI/administração & dosagem , Proteínas Ligadas por GPI/sangue , Proteínas Ligadas por GPI/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Lactoferrina/metabolismo , Lectinas/administração & dosagem , Lectinas/sangue , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Invasividade Neoplásica/patologia , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Ovário , Proteínas Recombinantes/administração & dosagem , Taxa de Sobrevida , Microambiente Tumoral
12.
Public Health ; 185: 130-138, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32622220

RESUMO

OBJECTIVES: Health insurance availability and affordability are vital elements in diagnosis and treatment of patients with cancer and thus constitute clinical significance as well. Although past studies have explored the disparity in mortality figures for patients with different insurance statuses, this population-based study is pioneering in analyzing the changes in cancer mortality risks over time amid macroeconomic shifts. STUDY DESIGN: The study uses Surveillance Epidemiology and End Results (SEER) data of 424,889 non-elderly patients with breast, cervical, ovarian, and uterine cancer diagnosed during 2007-2010 and 2011-2015. METHODS: In addition to discussing incidence figures and insurance patterns, the study uses Kaplan-Meier and Cox's proportional hazard models to examine the changes in survival probability and mortality risks for insurance-stratified patients with female-specific cancer across the two time periods. RESULTS: Patients without insurance have an increased risk of mortality over time relative to insured patients. Moreover, uninsured patients face this heightened risk more than Medicaid patients. DISCUSSION: Despite public policy measures as well as advancements in diagnostic facilities and treatment technology, the increased relative mortality of patients without insurance limits the long-term affordability of cancer treatment for economically vulnerable patients in comparison with insured patients.


Assuntos
Cobertura do Seguro/estatística & dados numéricos , Seguro Saúde/estatística & dados numéricos , Neoplasias/mortalidade , Adolescente , Adulto , Neoplasias da Mama/mortalidade , Feminino , Humanos , Incidência , Cobertura do Seguro/economia , Seguro Saúde/economia , Medicaid/economia , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/epidemiologia , Neoplasias Ovarianas/mortalidade , Fatores de Risco , Programa de SEER , Estados Unidos , Neoplasias do Colo do Útero/mortalidade , Neoplasias Uterinas/mortalidade , Adulto Jovem
13.
Int J Clin Oncol ; 25(9): 1726-1735, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32500467

RESUMO

BACKGROUND: This study investigated the pattern of first recurrence of advanced ovarian cancer before and after the introduction of aggressive surgery. METHODS: We investigated 291 patients with stage III/IV epithelial ovarian, fallopian tube, and peritoneal cancer. Aggressive surgery including gastrointestinal and upper abdominal surgeries was introduced for advanced ovarian cancer in 2008. The site and time until first recurrence were compared between 70 patients treated without aggressive surgery (2000-2007) and 221 patients who underwent aggressive surgery (2008-2016). RESULTS: The intraperitoneal recurrence rate was significantly lower in patients treated during 2008-2016 than in patients treated during 2000-2007 (55% [82/149] vs. 81% [46/57], p < 0.001). The median time to intraperitoneal recurrence was significantly longer during 2008-2016 than during 2000-2007 (36.2 months, 95% confidence interval [CI] 31.7-60.0 vs. 14.6 months, 95% CI 11.3-20.1, log-rank test: p < 0.001). However, extraperitoneal recurrence rate was significantly higher during 2008-2016 than during 2000-2007 (27% [40/149] vs. 2% [1/57], p < 0.001). Extraperitoneal recurrence occurred during 2008-2016 in the pleura/lungs and the para-aortic lymph nodes above the renal vessels. Cox proportional hazards regression analysis revealed that treatment period (HR 0.49, 95% CI 0.34-0.71, p < 0.001) and bevacizumab use (HR 0.58, 95% CI 0.39-0.87, p = 0.009) were independently associated with intraperitoneal recurrence; stage IV disease (HR 1.87, 95% CI 1.14-3.06, p = 0.034) was independently associated with extraperitoneal recurrence. CONCLUSION: Aggressive surgery reduced intraperitoneal recurrence and prolonged time to recurrence, contributing to better patient survival.


Assuntos
Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/secundário , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Feminino , Humanos , Linfonodos/patologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Estudos Retrospectivos
14.
Arch Gynecol Obstet ; 302(2): 481-486, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32519016

RESUMO

PURPOSE: To investigate the epidemiology, clinico-pathological characteristics and outcomes of patients diagnosed with malignant ovarian Sertoli-Leydig cell tumors (SLCTs) in comparison to granulosa cell tumors (GCTs). METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were accessed and patients diagnosed with a malignant SLCT and GCT between 1988 and 2013 were selected. Demographic and clinico-pathological characteristics were compared using the Mann-Whitney and chi-square tests. Overall (OS) and cancer-specific survival (CSS) rates were estimated with the Kaplan-Meier method and compared with the log-rank test. Cox hazard models were constructed to control for confounders. RESULTS: A total of 175 and 1361 patients diagnosed with SLCT and GCT, respectively, were identified. Compared to patients with GCT, those with SLCT were younger (median age 32 vs. 51 years, p < 0.001) and more likely to present with larger tumors (median size 15 vs 9.5 cm, p < 0.001) confined to the ovary (77.5% vs 69.2%, p = 0.031). Patients with SLCTs had worse CSS compared to those with GCTs, p < 0.001 (5-year rate was 76.2% vs 90.7%). After controlling for the presence of extra-ovarian disease and tumor size (≤ 10 vs > 10 cm), SCLTs were associated with a worse cancer-specific mortality compared to GCTs. CONCLUSIONS: SLCTs are extremely rare, commonly arise in premenopausal patients. They are associated with a poorer prognosis compared to GCT.


Assuntos
Tumor de Células da Granulosa/epidemiologia , Neoplasias Ovarianas/epidemiologia , Tumor de Células de Sertoli-Leydig/epidemiologia , Adulto , Feminino , Tumor de Células da Granulosa/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Tumor de Células de Sertoli-Leydig/mortalidade , Taxa de Sobrevida
15.
Expert Opin Pharmacother ; 21(13): 1579-1590, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32552175

RESUMO

Angiogenesis inhibitors have clearly shown activity in ovarian cancer in various settings; however, preliminary data did not reflect significant survival benefit. Bevacizumab has been extensively studied and is approved for use in ovarian malignancy. However, the efficacy of bevacizumab is modest and most treated patients eventually develop acquired resistance, which highlights the need for new targeted therapies and/or combination strategies. Newer therapies are being evaluated and their role of these newer therapies is upcoming and promising. Recent research focuses on the role of this drug group in frontline, maintenance and recurrent settings. Combination of PARP inhibitors with angiogenesis inhibitors has recently shown to improved survival rates. Potential strategies need to be devised for selecting patients most likely to benefit from such therapy.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Carcinoma Epitelial do Ovário/irrigação sanguínea , Carcinoma Epitelial do Ovário/mortalidade , Ensaios Clínicos como Assunto , Feminino , Humanos , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/mortalidade , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Resultado do Tratamento
16.
Zhonghua Zhong Liu Za Zhi ; 42(4): 331-335, 2020 Apr 23.
Artigo em Chinês | MEDLINE | ID: mdl-32375450

RESUMO

Objective: To investigate the clinicopathological characteristics and outcomes of a series of ovarian metastases of pancreatic ductal adenocarcinoma. Methods: Data of clinical manifestation, pathological characteristic, treatment and follow-up result from ten patients with ovarian metastases of pancreatic ductal adenocarcinoma confirmed by pathology were retrospectively analyzed. Results: The median age of onset was 46 years (38~79 years). The primary tumors were located in the body and tail of the pancreas in 8 cases. Bilateral ovarian metastasis occurred in 8 patients at the time of diagnosis. The median time from patients with clinical symptom to ovarian metastases was 2.5 months (0~12 months). Peritoneal metastasis was found in all of 10 cases. Nine cases were accompanied by CA125 elevation. The major features of metastatic carcinoma in the ovary were cystic-solid appearance (8 cases) and mucinous adenocarcinoma (6 cases) with no obvious immunohistochemical features in pathological observation. All patients underwent palliative ovariectomy at onset, and one patient underwent primary tumor resection simultaneously. Seven patients received chemotherapy. The median survival time of the 10 patients was 10.3 months. Conclusions: Ovarian metastases of pancreatic ductal adenocarcinoma are easily misdiagnosed. The final diagnosis depends on clinical manifestations, imaging and histopathological observation. Ovariectomy may be associated with better outcome.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Ductal Pancreático/patologia , Tumor de Krukenberg/patologia , Metástase Neoplásica/patologia , Neoplasias Ovarianas/patologia , Neoplasias Pancreáticas/patologia , Adenocarcinoma Mucinoso/mortalidade , Adulto , Idoso , Antígeno Ca-125/sangue , Carcinoma Ductal Pancreático/mortalidade , China/epidemiologia , Feminino , Humanos , Tumor de Krukenberg/mortalidade , Tumor de Krukenberg/secundário , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/secundário , Ovário/patologia , Estudos Retrospectivos
17.
Tumour Biol ; 42(5): 1010428320919198, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32364828

RESUMO

Detection of circulating tumor DNA is a new noninvasive technique with potential roles in diagnostic, follow-up, and prognostic evaluation of patients with many types of solid tumors. We aimed to evaluate the role of circulating tumor DNA in the setting of metastatic ovarian carcinoma. A prospective cohort of patients with metastatic ovarian cancer who were referred to systemic therapy was enrolled. Blood samples were collected before the start of treatment and monthly thereafter for 6 months. Circulating tumor DNA was quantified by real-time quantitative reverse transcription polymerase chain reaction of different lengths of Arthrobacter luteus elements as described by Umetani et al. A total of 11 patients were included, 2 for primary disease and 9 for recurrent disease. After the first cycle of chemotherapy, patients whose circulating tumor DNA levels increased from baseline were more likely to respond to chemotherapy than those whose circulating tumor DNA levels did not increase (p = 0.035). Furthermore, patients whose circulating tumor DNA levels rose after the first cycle of chemotherapy also had improved disease-free survival compared to those whose circulating tumor DNA levels did not increase (p = 0.0074). We conclude that the increase in circulating tumor DNA values collected in peripheral blood after the first cycle of systemic treatment in patients with advanced ovarian cancer is associated with an early response to systemic treatment and correlates with superior disease-free survival in this population. Circulating tumor DNA might be a specific, noninvasive, and cost-effective new biomarker of early response to systemic treatment in these patients.


Assuntos
Biomarcadores Tumorais , DNA Tumoral Circulante , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Idoso , Gerenciamento Clínico , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Projetos Piloto , Prognóstico , Tempo para o Tratamento , Resultado do Tratamento
18.
J Surg Oncol ; 122(3): 538-546, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32396667

RESUMO

BACKGROUND AND OBJECTIVES: We sought to explore the expression of mismatch repair (MMR) status and its correlation with clinicopathologic and survival characteristics in ovarian clear cell carcinoma (OCCC). METHODS: Expression of four MMR proteins (MLH1, PMS, MSH2, and MSH6) were measured using tissue microarray-based immunohistochemistry in 120 OCCC patients. The associations of clinicopathologic parameters with recurrence-free survival (RFS) and overall survival (OS) were analyzed by the Kaplan-Meier method, and multivariate analysis was further performed by the Cox regression model. RESULTS: Overall, 120 OCCC patients met the entry criteria, and their MMR status was detected, consisting of 24 patients with dMMR and 96 patients with proficient MMR (pMMR). Patients with dMMR were strongly associated with platinum-sensitive disease (P = .006) and large tumor volume (P = .038). Among all the patients who have received surgery, tumors with dMMR had a better RFS and OS than those with pMMR (hazard ratio [HR] for recurrence: 0.459 [95% confidence interval {95% CI} = 0.224-0.940], P = .029; HR for death: 0.381 [95% CI = 0.170-0.853], P = .015). In subgroup analysis, dMMR patients experienced a better trend of RFS (HR = 0.273; P = .055) and OS (HR = 0.165; P = .040) than pMMR cases among early stages (I-II), but this difference was not observed in advanced stage (III-IV) patients. Meanwhile, pMMR was associated with a more favorable trend of prognosis than dMMR in platinum-resistant patients (RFS: HR = 0.317, P = .051; OS: HR = 0.370, P = .046). Multivariate analysis revealed that only advanced stages (III-IV) were adverse independent prognosticators for both RFS (HR = 5.938 [95% CI = 2.804-12.574]; P < .001) and OS (HR = 6.209 [95% CI = 2.724-14.156]; P < .001). CONCLUSION: Tumors with dMMR were related to better OS in OCCC on univariate analysis. Only the tumor stage was an independent prognosticator for both RFS and OS. MMR status is a potentially valuable prognostic index in OCCC patients, and larger prospective studies are required to validate its prognostic role.


Assuntos
Adenocarcinoma de Células Claras/genética , Adenocarcinoma de Células Claras/patologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Reparo de Erro de Pareamento de DNA , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Adenocarcinoma de Células Claras/metabolismo , Adenocarcinoma de Células Claras/mortalidade , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/mortalidade , Proteínas de Ligação a DNA/biossíntese , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/biossíntese , Proteína 1 Homóloga a MutL/biossíntese , Proteína 2 Homóloga a MutS/biossíntese , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/mortalidade , Análise Serial de Tecidos
19.
Am J Surg Pathol ; 44(8): 1050-1060, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32384321

RESUMO

The prevalence and significance of programmed death-1 ligand (PD-L1) expression in different types of tubo-ovarian carcinoma have not been well defined. We evaluated PD-L1 expression and CD8 tumor-infiltrating lymphocyte (TIL) density in whole tissue sections of 189 cases of tubo-ovarian carcinoma, including high-grade serous carcinoma (HGSC, n=100), clear cell carcinoma (CCC, n=24), endometrioid carcinoma (EmC, n=40), and mucinous carcinomas (MC, n=25). Using the tumor proportion score (TPS) with a 1% cutoff, PD-L1 expression was present in 21% of HGSC, 16.7% of CCC, 2.5% of EmC, and 4% of MC. Using the combined positive score (CPS) with a cutoff of 1, PD-L1 expression was present in 48% of HGSC, 25% of CCC, 20% of EmC, and 24% of MC. HGSC demonstrated significantly higher CD8 TIL density than CCC (P=0.013238), EmC (P=0.01341), or MC (P=0.004556). In HGSC, CD8 TIL density was directly correlated with PD-L1 positivity using either TPS (P=0.0008) or CPS (P=0.00011). Survival analysis of patients with high stage (stage III to IV) HGSC revealed PD-L1 positivity by TPS to be associated with improved progression-free survival (adjusted hazard ratio: 0.4912 vs. 2.036, P=0.0378). Although not statistically significant, a similar trend was observed in overall survival (adjusted hazard ratio: 0.3387 vs. 2.953, P=0.0548). In contrast, with CPS, no significant difference was identified between PD-L1-positive and negative groups in either progression-free survival (P=0.5086) or overall survival (P=0.7823). Neoadjuvant chemotherapy was associated with higher PD-L1 expression by TPS (P=0.00407) but not CPS. No significant difference in PD-L1 expression was detected in tumors from patients with germline BRCA1/2 mutations compared with germline mutation-negative tumors by either TPS or CPS. In conclusion, the prevalence of PD-L1 expression is variable in different types of tubo-ovarian carcinoma and is highest in HGSC. In high-stage HGSC, PD-L1 positivity in tumor cells is associated with an increased immune response and improved survival.


Assuntos
Adenocarcinoma de Células Claras/imunologia , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Linfócitos T CD8-Positivos/imunologia , Carcinoma Endometrioide/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Císticas, Mucinosas e Serosas/imunologia , Neoplasias Ovarianas/imunologia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Endometrioide/mortalidade , Carcinoma Endometrioide/patologia , Carcinoma Endometrioide/terapia , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Císticas, Mucinosas e Serosas/mortalidade , Neoplasias Císticas, Mucinosas e Serosas/patologia , Neoplasias Císticas, Mucinosas e Serosas/terapia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Intervalo Livre de Progressão , Fatores de Tempo , Adulto Jovem
20.
Int J Gynaecol Obstet ; 150(2): 169-176, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32415982

RESUMO

OBJECTIVE: To evaluate long-term outcomes after surgery for apparent early-stage ovarian cancer (OC). METHODS: Retrospective analysis of women who underwent staging surgery for apparent early-stage OC at a single center in Milan, Italy, from 1990 to 2008, and had a follow-up longer than 10 years (living women with no recurrence). Univariate and multivariate analyses and propensity score matching were carried out. RESULTS: Overall, 182 women underwent radical (n=148, 81.3%) or conservative (n=34, 18.7%) procedures for early-stage OC. Ten-year disease-free and overall survival were 82.9% (n=151) and 87.9% (n=160), respectively. Conservative or radical surgery had similar disease-free (log-rank test, P=0.783) and overall (log-rank test, P=0.783) survival. These data were confirmed after the application of propensity score matching. High-risk features correlated with non-significant worse disease-free survival (P=0.080). In the high-risk group (≥Grade 3 or ≥ Stage IC), type of surgical approach (conservative vs radical) did not affect survival (hazard ratio, 0.81; 95% confidence interval, 0.18-3.56; P=0.781). CONCLUSION: Women with early-stage OC had encouraging long-term survival. The presence of high-risk disease had detrimental effects on survival, regardless of surgical approach. High-risk disease should not be considered a contraindication to conservative surgery.


Assuntos
Tratamento Conservador/mortalidade , Intervalo Livre de Doença , Neoplasias Ovarianas/cirurgia , Adulto , Estudos de Casos e Controles , Tratamento Conservador/métodos , Feminino , Seguimentos , Humanos , Itália , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias/métodos , Neoplasias Ovarianas/mortalidade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos
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