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1.
Medicine (Baltimore) ; 99(11): e19372, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176061

RESUMO

OBJECTIVE: Apatinib mesylate is a novel vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, which has exhibited good safety and efficacy in several types of solid tumors. The present study aimed to assess the clinical efficacy and safety of apatinib combined with chemotherapy and concurrent chemo-brachytherapy (CCBT) in patients with recurrent and advanced cervical cancer. METHODS: A total of 52 patients with first diagnosed recurrent or untreated International Federation of Gynecology and Obstetrics stage IVB cervical cancer admitted at Shandong Cancer Hospital and Institute between July 2016 and May 2018 were analyzed in the current randomized controlled trial. The patients were randomly divided into 2 groups: the apatinib-treated group and the control group. Patients with recurrent cervical cancer in the apatinib-treated group were administered apatinib and carboplatin-paclitaxel as first-line chemotherapy. Patients with advanced cervical cancer were administered apatinib in combination with CCBT. In control group, patients with recurrent cervical cancer were treated with chemotherapy alone while patients with advanced cervical cancer received CCBT. RESULTS: The progression-free survival was significantly prolonged in apatinib group compared with control group (10.1 months; 95% confidence interval (CI), 8.42-11.79 vs 6.4 months; 95% CI, 3.88-8.92; P < .01; hazard ratio (HR), 0.44; 95% CI, 0.25-0.78; P < .01). The objective response rate in apatinib group was obviously higher than that in control group (64.3% vs 33.3%, P < .05). Proteinuria, hand-foot syndrome, mucositis, and hypertension in all Grades were statistically more common in apatinib group than in control group. Apatinib did not obviously aggravate other radiotherapy or chemotherapy side effects. CONCLUSION: Apatinib exhibited promising clinical efficacy in cervical cancer patients, resulting in an improved response rate and prolonged progression-free survival compared with the control group, and had manageable side effects. Our study revealed that apatinib combination therapy, adenocarcinoma, and bone metastasis.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Braquiterapia/métodos , Recidiva Local de Neoplasia/terapia , Piridinas/uso terapêutico , Neoplasias do Colo do Útero/terapia , Adulto , Quimiorradioterapia/métodos , China , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
2.
Medicine (Baltimore) ; 99(11): e18668, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176025

RESUMO

This study aimed to compare the sirtuin 2 (SIRT2) expression between tumor tissue and adjacent tissue, and to investigate the association of tumor SIRT2 expression with clinical characteristics and survival profiles in cervical cancer patients.One hundred ninety-one cervical cancer patients were reviewed in this retrospective study. All patients underwent surgical resection and had well-preserved tumor tissue and adjacent tissue, which were obtained for SIRT2 expression detection by immunohistochemistry (IHC). Clinical parameters were obtained. Disease free survival (DFS) and overall survival (OS) were calculated.Both SIRT2 expression by IHC score (P < .001) and the percentage of SIRT2 high expression (defined as IHC score >3) (P < .001) were declined in tumor tissue compared with paired adjacent tissue. In addition, SIRT2 expression in tumor tissue was negatively correlated with tumor size (P = .047), lymph node metastasis (P = .009) and FIGO stage (P = .001). And the DFS (P = .007) as well as OS (P = .008) were better in patients with SIRT2 high expression compared with patents with SIRT2 low expression. Univariate Cox's proportional hazards regression model analyses revealed that high SIRT2 expression in tumor tissue was a predictive factor for more prolonged DFS (P = .009) and OS (P = .011), while multivariate Cox's proportional hazards regression model analysis disclosed that it lacks independent predictive value for DFS (P = .084) or OS (P = .132).SIRT2 expression exhibits potential to serve as a biomarker for disease surveillance and prognosis in the management of cervical cancer patients.


Assuntos
Sirtuína 2/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Adulto , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Colo do Útero/metabolismo , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sirtuína 2/análise , Análise de Sobrevida , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/mortalidade
3.
Medicine (Baltimore) ; 99(11): e19131, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176038

RESUMO

A collision tumor is defined by co-existence of two adjacent tumors which are histologically distinct. Little is known about the clinical manifestation, treatment, and prognosis of cervical collision cancer. The objective of the study was to investigate the management and prognosis of patients with cervical collision cancer.We retrospectively reviewed and enrolled patients with cervical collision carcinoma from 2010 to 2018 in two institutions (West China Hospital and West China Second University Hospital). The clinical presentation, pathology, treatment, and prognosis of patients with collision carcinoma of the uterine cervix were retrospectively reviewed. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method.A total of 24 patients were included in this study. The proportion of cervical collision carcinoma was 0.4% in the cervical carcinoma cohort (24/6015). The median age of the patients with cervical collision cancer was 42 years. The most common presenting symptom was cervical contactive bleeding. There were 23 patients classified as International Federation of Gynecology and Obstetrics (FIGO) stage IA1-IIB. All patients except one received radical hysterectomy, in which 21 patients received bilateral salpingo-oophorectomy (BSO) and pelvic lymphadenectomy in addition. There were 16 patients who received adjuvant chemotherapy or chemoradiotherapy. The median follow-up time was 21 months. No patient death was observed. Recurrence only occurred in two patients. The 5-year OS rates and PFS rates were 100% and 91.7%, respectively.This study revealed that cervical collision cancer was a type of rare cervical cancer with good prognosis. Cervical collision cancer responded well to the same treatment methods as the cervical squamous cell carcinoma and was associated with few recurrence and long survival.


Assuntos
Neoplasias Primárias Múltiplas/patologia , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , China , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/terapia , Panicum , Intervalo Livre de Progressão , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia
4.
Lancet ; 395(10224): 591-603, 2020 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-32007142

RESUMO

BACKGROUND: WHO is developing a global strategy towards eliminating cervical cancer as a public health problem, which proposes an elimination threshold of four cases per 100 000 women and includes 2030 triple-intervention coverage targets for scale-up of human papillomavirus (HPV) vaccination to 90%, twice-lifetime cervical screening to 70%, and treatment of pre-invasive lesions and invasive cancer to 90%. We assessed the impact of achieving the 90-70-90 triple-intervention targets on cervical cancer mortality and deaths averted over the next century. We also assessed the potential for the elimination initiative to support target 3.4 of the UN Sustainable Development Goals (SDGs)-a one-third reduction in premature mortality from non-communicable diseases by 2030. METHODS: The WHO Cervical Cancer Elimination Modelling Consortium (CCEMC) involves three independent, dynamic models of HPV infection, cervical carcinogenesis, screening, and precancer and invasive cancer treatment. Reductions in age-standardised rates of cervical cancer mortality in 78 low-income and lower-middle-income countries (LMICs) were estimated for three core scenarios: girls-only vaccination at age 9 years with catch-up for girls aged 10-14 years; girls-only vaccination plus once-lifetime screening and cancer treatment scale-up; and girls-only vaccination plus twice-lifetime screening and cancer treatment scale-up. Vaccination was assumed to provide 100% lifetime protection against infections with HPV types 16, 18, 31, 33, 45, 52, and 58, and to scale up to 90% coverage in 2020. Cervical screening involved HPV testing at age 35 years, or at ages 35 years and 45 years, with scale-up to 45% coverage by 2023, 70% by 2030, and 90% by 2045, and we assumed that 50% of women with invasive cervical cancer would receive appropriate surgery, radiotherapy, and chemotherapy by 2023, which would increase to 90% by 2030. We summarised results using the median (range) of model predictions. FINDINGS: In 2020, the estimated cervical cancer mortality rate across all 78 LMICs was 13·2 (range 12·9-14·1) per 100 000 women. Compared to the status quo, by 2030, vaccination alone would have minimal impact on cervical cancer mortality, leading to a 0·1% (0·1-0·5) reduction, but additionally scaling up twice-lifetime screening and cancer treatment would reduce mortality by 34·2% (23·3-37·8), averting 300 000 (300 000-400 000) deaths by 2030 (with similar results for once-lifetime screening). By 2070, scaling up vaccination alone would reduce mortality by 61·7% (61·4-66·1), averting 4·8 million (4·1-4·8) deaths. By 2070, additionally scaling up screening and cancer treatment would reduce mortality by 88·9% (84·0-89·3), averting 13·3 million (13·1-13·6) deaths (with once-lifetime screening), or by 92·3% (88·4-93·0), averting 14·6 million (14·1-14·6) deaths (with twice-lifetime screening). By 2120, vaccination alone would reduce mortality by 89·5% (86·6-89·9), averting 45·8 million (44·7-46·4) deaths. By 2120, additionally scaling up screening and cancer treatment would reduce mortality by 97·9% (95·0-98·0), averting 60·8 million (60·2-61·2) deaths (with once-lifetime screening), or by 98·6% (96·5-98·6), averting 62·6 million (62·1-62·8) deaths (with twice-lifetime screening). With the WHO triple-intervention strategy, over the next 10 years, about half (48% [45-55]) of deaths averted would be in sub-Saharan Africa and almost a third (32% [29-34]) would be in South Asia; over the next 100 years, almost 90% of deaths averted would be in these regions. For premature deaths (age 30-69 years), the WHO triple-intervention strategy would result in rate reductions of 33·9% (24·4-37·9) by 2030, 96·2% (94·3-96·8) by 2070, and 98·6% (96·9-98·8) by 2120. INTERPRETATION: These findings emphasise the importance of acting immediately on three fronts to scale up vaccination, screening, and treatment for pre-invasive and invasive cervical cancer. In the next 10 years, a one-third reduction in the rate of premature mortality from cervical cancer in LMICs is possible, contributing to the realisation of the 2030 UN SDGs. Over the next century, successful implementation of the WHO elimination strategy would reduce cervical cancer mortality by almost 99% and save more than 62 million women's lives. FUNDING: WHO, UNDP, UN Population Fund, UNICEF-WHO-World Bank Special Program of Research, Development and Research Training in Human Reproduction, Germany Federal Ministry of Health, National Health and Medical Research Council Australia, Centre for Research Excellence in Cervical Cancer Control, Canadian Institute of Health Research, Compute Canada, and Fonds de recherche du Québec-Santé.


Assuntos
Neoplasias do Colo do Útero/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Países em Desenvolvimento , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Renda , Lactente , Recém-Nascido , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Modelos Biológicos , Mortalidade/tendências , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Vacinação/métodos , Organização Mundial da Saúde , Adulto Jovem
5.
Bull Cancer ; 107(3): 322-327, 2020 Mar.
Artigo em Francês | MEDLINE | ID: mdl-32061377

RESUMO

Cervical cancer screening is considered one of the most significant public health interventions that can reduce not only the incidence, but also the mortality of the disease. One of the most important factors for screening effectiveness is coverage defined as the number of women tested within a recommended interval. In the first years of the cervical screening, the participation rate in National Screening Program in Romania was 14.2% with slight difference in different region of the country. In the northeastern part of the country, in the first four years of the program, the rate was 16.9% with an alarmingly continuous decrease. Thus, increasing the rate of uptake of cervical screening is essential. The policy-makers should take new measures to increase women's participation in this screening program. The objective of this paper was to review situation of the screening program and to identify gaps and needs in the system and to bring or suggest solution.


Assuntos
Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Participação do Paciente/estatística & dados numéricos , Avaliação de Programas e Projetos de Saúde , Neoplasias do Colo do Útero/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Detecção Precoce de Câncer/tendências , Feminino , Educação em Saúde/métodos , Humanos , Disseminação de Informação , Programas de Rastreamento/organização & administração , Programas de Rastreamento/estatística & dados numéricos , Programas de Rastreamento/tendências , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Participação do Paciente/tendências , Avaliação de Programas e Projetos de Saúde/estatística & dados numéricos , Romênia/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/virologia
6.
Anticancer Res ; 40(2): 999-1006, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014945

RESUMO

BACKGROUND/AIM: We aimed to evaluate the efficacy of high-dose-rate brachytherapy techniques selected according to pre-brachytherapy magnetic resonance imaging (MRI) findings in asymmetrical cervical cancer (ACC). PATIENTS AND METHODS: We analyzed 33 ACC patients. Asymmetric tumors were defined as those in which the difference between the distance from the cervical canal to the farthest end of the tumor [long distance (LD)] and the distance from the cervical canal to the contralateral tumor edge [short distance (SD)] is equal to or greater than 2 cm on the basis of MRI prior to treatment. On pre-treatment and pre-brachytherapy MRI, the median LDs were 40 mm and 21 mm, respectively. Patients with LD≥2 cm and LD - SD≥1 cm on pre-brachytherapy MRI received non-conventional intracavitary brachytherapy (ICBT). RESULTS: Sixteen patients (48%) received non-conventional ICBT. There was no significant difference in 3-year local control between the two treatment groups (100% vs. 81.2%, p=0.07); two patients had grade 2 radiation proctitis. CONCLUSION: Brachytherapy techniques selected according to pre-brachytherapy MRI findings were effective for ACC treatment.


Assuntos
Braquiterapia , Dosagem Radioterapêutica , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Braquiterapia/efeitos adversos , Braquiterapia/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Resultado do Tratamento , Neoplasias do Colo do Útero/diagnóstico
7.
J Surg Oncol ; 121(4): 620-629, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31970787

RESUMO

BACKGROUND AND OBJECTIVES: Recent studies demonstrating decreased survival following minimally invasive surgery (MIS) for cervical cancer have generated concern regarding oncologic efficacy of MIS. Our objective was to evaluate the association between surgical approach and 5-year survival following resection of abdominopelvic malignancies. METHODS: Patients with stage I or II adenocarcinoma of the prostate, colon, rectum, and stage IA2 or IB1 cervical cancer from 2010-2015 were identified from the National Cancer Data Base. The association between surgical approach and 5-year survival was assessed using propensity-score-matched cohorts. Distributions were compared using logistic regression. Hazard ratio for death was estimated using Cox proportional-hazard models. RESULTS: The rate of deaths at 5 years was 3.4% following radical prostatectomy, 22.9% following colectomy, 18.6% following proctectomy, and 6.8% following radical hysterectomy. Open surgery was associated with worse survival following radical prostatectomy (HR, 1.18; 95% CI, 1.05-1.33; P = .005), colectomy (HR, 1.45; 95% CI, 1.39-1.51; P < .001), and proctectomy (HR, 1.28; 95% CI, 1.10-1.50; P = .002); however, open surgery was associated with improved survival following radical hysterectomy (HR, 0.61; 95% CI, 0.44-0.82; P = .003). CONCLUSIONS: These results suggest that MIS is an acceptable approach in selected patients with prostate, colon, and rectal cancers, while concerns regarding MIS resection of cervical cancer appear warranted.


Assuntos
Neoplasias Abdominais/mortalidade , Neoplasias Abdominais/cirurgia , Neoplasias Pélvicas/mortalidade , Neoplasias Pélvicas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/cirurgia , Idoso , Colectomia/mortalidade , Colectomia/estatística & dados numéricos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Feminino , Humanos , Histerectomia/mortalidade , Histerectomia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Protectomia/mortalidade , Protectomia/estatística & dados numéricos , Prostatectomia/mortalidade , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/cirurgia , Neoplasias Retais/mortalidade , Neoplasias Retais/cirurgia , Análise de Sobrevida , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/cirurgia
8.
Int J Radiat Oncol Biol Phys ; 106(2): 310-319, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682968

RESUMO

PURPOSE: This phase II study evaluated the utility of magnetic resonance imaging (MRI) and positron emission tomography for planning radiation and brachytherapy in patients with postsurgical recurrence of cervical cancer. METHODS AND MATERIALS: The study (NCT01391065) recruited patients with residual or recurrent disease after hysterectomy. Patients underwent baseline T2 weighted (T2W) MRI, 18F-flouro-deoxyglucose (18F-FDG), 18F-flouro thymidine (18F-FLT) and 18F-flouromisonidazole (18F-F Miso) positron emission tomography (PET) and received external radiation (50 Gy/25 fractions for 5 weeks) and weekly cisplatin (40 mg/m2). MRI was performed at brachytherapy and used for delineation of clinical target volume (CTV). Patients with parametrial disease at baseline received interstitial brachytherapy (16-20 Gy/4-5 fractions) and those with vaginal disease received intracavitary brachytherapy (12-14 Gy/2-4 fractions). Kaplan-Meier analysis was performed to evaluate locoregional relapse, disease free survival, and overall survival. Common Toxicity Criteria for adverse event reporting (CTCAE) v4.1 was used for toxicity scoring and European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questtionaire Core 30 (QLQC-30) and Cx 24 for quality-of-life reporting. RESULTS: Between January 2011 and February 2016, 60 patients were included, of which 50 received study treatment. The mean gross tumor volume on T2 W MR was 20 (IQR 3.6-90) cc. The metabolic tumor volume was 15 (interquartile range [IQR] 2.1-56.1) cc. The median FLT volume was 10 (IQR 0-48) cc. A total of 8 patients had 18-F F Miso uptake. The median CTV at brachytherapy was 38 (12-85) cc. The median CTVD90 and D 98 was 71 (53-74) and 74 (53-74) Gy. At a median follow-up of 60 (5-93) months, the 5-year local control, disease free survival, and overall survival were 84%, 73%, and 74.5%, respectively. Grade III and IV proctitis and cystitis were observed in 4% and 2% of patients. On multivariate analysis baseline tumor volume, on T2 W MR impacted disease free (91% vs 65%, P = .03) and overall survival (96% vs 77%, P = .06). CONCLUSIONS: Image-guided assisted radiation and brachytherapy are associated with good to excellent local control and survival in patients with vaginal recurrences of cervical cancer.


Assuntos
Braquiterapia/métodos , Recidiva Local de Neoplasia/radioterapia , Radioterapia Guiada por Imagem/métodos , Neoplasias do Colo do Útero/radioterapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Braquiterapia/efeitos adversos , Cisplatino/uso terapêutico , Cistite/etiologia , Cistite/patologia , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/mortalidade , Neoplasia Residual , Tomografia por Emissão de Pósitrons/métodos , Proctite/etiologia , Proctite/patologia , Estudos Prospectivos , Qualidade de Vida , Compostos Radiofarmacêuticos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/efeitos adversos , Carga Tumoral , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia
9.
Int J Cancer ; 146(7): 1993-2006, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31709528

RESUMO

Regulatory T cells (Tregs) are crucial for the maintenance of peripheral tolerance, but they also limit beneficial responses through cancer-induced immunoediting. The roles of Treg subsets in cervical squamous cell carcinoma (CSCC) are currently unknown. Here, we aimed to perform an extensive study with an increased resolution of the Treg compartment in the peripheral blood and tumor tissues of CSCC patients. We first identified that an HLADRhi Treg population in the peripheral blood was significantly increased in CSCC patients compared to precancer patients and healthy donors. We found that HLADRhi Tregs express high levels of a panel of inhibition and activation markers and the TCR-responsive transcription factors BATF and IRF4. However, this Treg subset showed reduced calcium influx after TCR crosslinking. In addition, HLADRhi Tregs are highly proliferative and vulnerable to apoptosis. Further studies demonstrated that the HLADRhi Tregs display high levels of suppressive activity. Quantitative multiplexed immunohistochemistry revealed that an increase in the number of tumor-infiltrating HLADRhi Tregs is associated with unfavorable classical risk parameters of advanced disease stage and stromal invasion. Context-based quantification revealed that a high frequency of stromal HLADRhi Tregs in patients is significantly associated with worse progression-free survival. In the current study, we characterized a population of highly activated and immunosuppressive HLADRhi Tregs in CSCC patients. An increased HLADRhi Treg frequency may be a potential biomarker to stratify CSCC patients and evaluate therapeutic efficacies in personalized immuno-oncology studies.


Assuntos
Antígenos HLA-DR/metabolismo , Imunomodulação , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/metabolismo , Apoptose , Biomarcadores , Progressão da Doença , Feminino , Antígenos HLA-DR/imunologia , Humanos , Imuno-Histoquímica , Ativação Linfocitária , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/patologia , Fenótipo , Prognóstico , Microambiente Tumoral/imunologia , Neoplasias do Colo do Útero/mortalidade
10.
Oncology ; 98(2): 91-97, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31593942

RESUMO

OBJECTIVE: At the end of the year 2018, a new FIGO classification for cervical cancer was published, mainly revising stage IB and introducing a new stage IIIC, which includes irrespectively of tumor size and local spread all patients with lymph node metastasis. METHODS: We retrospectively analyzed all cases of cervical cancer stage I to IIB who underwent surgery as primary treatment at our institution from 2000 until 2016 and therefore had a histological confirmation of tumor stage. We reclassified all histologies according to the new FIGO classification and calculated outcome according to the new stages. RESULTS: Out of 265 patients, 146 (55%) patients were reclassified into a higher FIGO stage. Most changes appeared within stage IB and from any stage to stage IIIC1. Kaplan-Meier curves for new stages showed a significant difference in disease-free survival (DFS) and overall survival (OS) between stages I versus II versus III (log-rank test, both p < 0.001). Overall, patients that were upstaged had a significant worse DFS (p = 0.012) and OS (p = 0.008) than patients whose stage did not change. Similar observations were made within sub-stages, when node-positive IB or IIB tumors were upstaged to IIIC tumors. CONCLUSION: The new FIGO classification for cervical cancer reflects the strong impact of lymph node metastases on survival and is a clear improvement compared to the old FIGO classification with regard to risk stratification.


Assuntos
Estadiamento de Neoplasias/métodos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos
11.
Int J Cancer ; 146(7): 2047-2058, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732968

RESUMO

More than one-third of patients with locally advanced cervical cancer do not respond to chemoradiation therapy (CRT). We aimed to characterize the transcriptional landscape of paired human cervical tumors before and during CRT in order to gain insight into the evolution of treatment response and to elucidate mechanisms of treatment resistance. We prospectively collected cervical tumor biopsies from 115 patients both before and 3 weeks into CRT. RNA-sequencing, Gene Set Enrichment Analysis and HPV gene expression were performed on 20 paired samples that had adequate neoplastic tissue mid-treatment. Tumors from patients with no evidence of disease (NED) at last follow-up had enrichment in pathways related to the immune response both pretreatment and mid-treatment, while tumors from patients dead of disease (DOD) demonstrated enrichment in biosynthetic and mitotic pathways but not in immune-related pathways. Patients DOD had decreased expression of T-cell and cytolytic genes and increased expression of PD-L2 mid-treatment compared to patients NED. Histological and immunohistochemical analysis revealed a decrease in tumor-associated lymphocytes (TAL) during CRT in all patients but tumors from patients DOD had a significantly more pronounced decrease in TALs and CD8+ cells mid-treatment, which was validated in a larger mid-treatment cohort. Finally, patients DOD retained more HPV E6/E7 gene expression during CRT and this was associated with increased expression of genes driving mitosis, which was corroborated in vitro. Our results suggest that decreased local immune response and retained HPV gene expression may be acting together to promote treatment resistance during CRT in patients with cervical cancer.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Regulação Viral da Expressão Gênica , Imunomodulação/efeitos dos fármacos , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos/imunologia , Feminino , Perfilação da Expressão Gênica , Humanos , Metástase Linfática , Estadiamento de Neoplasias , Papillomaviridae/classificação , Papillomaviridae/imunologia , Infecções por Papillomavirus/imunologia , Prognóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/mortalidade
12.
Cancer Treat Rev ; 83: 101945, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838220

RESUMO

PURPOSE: Neoadjuvant chemotherapy followed by surgery (NACT + S) has been compared with definitive chemoradiothherapy (CRT) in randomized clinical trials (RCTs) in stage IB2, IIA and IIB cervical cancer (1994 Figo stage). Our aim was to evaluate efficacy and toxicity of NACT + S and CRT and identify differences in clinical outcomes and severe toxicity frequency. METHODS: The PRISMA statement was applied. Random-effects models were used. RESULTS: Two RCTs representing 1259 patients were identified. NACT + S was not associated with significant OS improvement compared with CRT, with HR of 1.08 (95% CI = 0.86-1.36; p = 0.51). The HR of relapse was 1.32 (95%CI = 1.07-1.62) in favor of CRT. Severe acute toxicity was lower in CRT group. CONCLUSION: This meta-analysis showed similar OS rates between treatment and CRT superiority over NACT + S in terms of DFS and severe acute toxicity. Impact on long term toxicity and quality of life remain to be proven.


Assuntos
Quimiorradioterapia/mortalidade , Quimioterapia Adjuvante/mortalidade , Histerectomia/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias do Colo do Útero/mortalidade , Terapia Combinada , Feminino , Humanos , Prognóstico , Taxa de Sobrevida , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
13.
Orv Hetil ; 160(49): 1948-1956, 2019 Dec.
Artigo em Húngaro | MEDLINE | ID: mdl-31786940

RESUMO

Introduction: The organized breast and cervical screening programs were implemented in the framework of public health program in Hungary in order to reduce breast cancer mortality by 30% and cervical cancer mortality by 60% in given age groups within 10 years by 2012. Aim: The aim of our study was to conduct a retrospective analysis of mortality and morbidity data and to evaluate the effectiveness of the implemented screening programs. Method: Descriptive statistical analysis was performed by age-standardized mortality and morbidity data between 1980 and 2015 with special regard to the period of 2002-2012. Results: Breast cancer mortality of women aged 45-64 reduced by 28.3%, the incidence reduced by 23.6% and the incidence of in situ carcinoma increased by 242% between 2002 and 2012. Cervical cancer mortality of women aged 25-64 years reduced by 25.5%, the incidence reduced by 21.2%, and the incidence of in situ carcinoma increased by 13.3% during 2002-2012. Conclusion: Although both breast cancer and cervical cancer mortality substantially decreased in Hungary, the decrease in cervical cancer did not reach the target value. Orv Hetil. 2019; 160(49): 1948-1956.


Assuntos
Neoplasias da Mama/mortalidade , Detecção Precoce de Câncer/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Hungria/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias do Colo do Útero/diagnóstico
14.
Adv Clin Exp Med ; 28(10): 1377-1383, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31638746

RESUMO

BACKGROUND: Poland is considered among the European countries with an average incidence of cervical cancer (CC; about 3,000-3,500/year) and at the same time with high mortality (5-year survival rate - 55.2%). For this reason, in 2006 Poland introduced a Population-Based Cervical Cancer Prevention and Early Detection Program addressed to women aged 25-59 years, in which a cytological test is carried out every 3 years. OBJECTIVES: The aim of the study was to assess the changes in the curability of CC patients brought by the introduction of the Screening Program in the Lower Silesian voivodeship and to identify the subpopulation of women for whom activities aimed at increasing adherence rates must be intensified. MATERIAL AND METHODS: The 5-year relative survival in 3,586 CC patients from 2000-2010 registered in the Lower Silesian Cancer Registry was analyzed. RESULTS: In the Lower Silesian voivodeship, a 55.1% 5-year survival rate was recorded in 2000-2004 and 70.5% in 2010. The highest increase in 5-year relative survival rates was found in rural communities (from 53.1% in 2000-2004 to 77.7% in 2010) and in Wroclaw (56.8% and 74.2%, respectively). In the study group, the number of patients with invasive CC (C53) detected in the local stage of the disease increased systematically from 61.5% in 2000-2004 to 74.3% in 2010. CONCLUSIONS: The introduction of the population-based screening program improved the curability rate in CC patients in the Lower Silesian voivodeship. In order to maintain the recent positive trends, further education should be continued, and activities aimed at increasing adherence to screening tests should be intensified, especially in urban-rural communities.


Assuntos
Programas de Rastreamento/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Cooperação do Paciente/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Detecção Precoce de Câncer , Feminino , Humanos , Incidência , Masculino , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Cooperação do Paciente/psicologia , Polônia/epidemiologia , Vigilância da População , Avaliação de Programas e Projetos de Saúde , Taxa de Sobrevida/tendências , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia
15.
Medicine (Baltimore) ; 98(40): e17301, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577720

RESUMO

The metastasis of cervical carcinoma is associated with the lymphovascular spread. The primary objective of the present study was to determine the prognostic value of lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer in Jilin, China.In this retrospective cohort study, patients with early-stage cervical cancer (stage IB-IIA) at the Second Hospital of Jilin University from February 2014 to December 2016 were included in the analysis. All included participants underwent radical hysterectomy with pelvic lymphadenectomy. LVSI was identified by hematoxylin and eosin (H&E) staining. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Kaplan-Meier curves were used to calculate the patient's survival. Survival was compared using the log-rank test, while risk factors for the prognosis were assessed by Cox regression analysis.The incidence of LVSI was positively associated with the depth of stromal invasion (P = .009) and lymph node metastasis (LNM, P < .001). LVSI is an independent factor that affects OS (P = .009) and PFS (P = .006) in patients with early stage cervical cancer. LNM status is an independent factor that affects postoperative OS (P = .005).The incidence of lymphatic vessel infiltration is positively associated with the depth of stromal invasion and LNM. LVSI is an independent risk factor for the prognosis of early cervical cancer. The results suggest that further large-scale studies are needed to improve the treatment for patients with LVSI.


Assuntos
Metástase Linfática/patologia , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto , China/epidemiologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/terapia
16.
Medicine (Baltimore) ; 98(39): e17234, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574835

RESUMO

Locally advanced cervical carcinoma has a poor prognosis. Neoadjuvant chemotherapy (NACT) can reduce tumor size and improve tumor resection rate, but its use in large locally advanced cervical carcinoma is controversial. This study aimed to evaluate the treatment and prognosis of NACT in patients with cervical carcinoma stage IB2 or IIA2.This was a retrospective cohort study of patients who underwent type-C radical surgery and pelvic lymphadenectomy due to cervical carcinoma stage IB2/IIA2 between 2/2014 and 12/2016 at the Second Hospital of Jilin University. The patients were grouped according to whether they received NACT (paclitaxel and a platinum salt) or not. Overall survival (OS) and progression-free survival (PFS) were compared between the 2 groups.Of the 144 patients, 60 (41.7%) received NACT. A total of 119 patients underwent postoperative radiation therapy, of which 97 received radiation therapy alone and 22 received concurrent chemoradiotherapy. The adverse reactions in the NACT group were mainly hematologic toxic reactions, but were tolerated. No grade ≥III adverse reactions were observed. NACT did not significantly affect the PFS (P = .453) and OS (P = .933) between the 2 groups. No factor was found to be independently associated with OS or PFS (all P > .05).Compared with patients who underwent surgery with/without radiotherapy and/or chemotherapy, NACT using paclitaxel and a platinum salt does not improve the prognosis and lymph node metastasis rate of locally advanced cervical carcinoma in Chinese patients.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/mortalidade , Histerectomia/mortalidade , Terapia Neoadjuvante/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adulto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia/mortalidade , China , Feminino , Seguimentos , Humanos , Histerectomia/métodos , Excisão de Linfonodo/mortalidade , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Paclitaxel/administração & dosagem , Prognóstico , Intervalo Livre de Progressão , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia
17.
Cell Biochem Funct ; 37(8): 591-597, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31512281

RESUMO

Cervical cancer is still a serious threat to women's health and life safety worldwide, and new treatment strategies are urgently needed. Accumulating evidences also imply that long non-coding RNAs (lncRNAs) are involved in a wide range of cellular processes, such as cell proliferation, apoptosis, and cell cycle. We found that the expression of lncOGFRP1 in cervical cancer tissues was significantly higher than that in normal cervical tissues (P < .05). Further, CCK8 detection found when lncOGFRP1 was silenced, the proliferation of cells was inhibited. After depleting lncOGFRP1, the proportion of apoptosis cells in C33A (3.71 ± 0.38% VS 11.98 ± 1.26%, P < .05) and SiHa (0.69 ± 0.06% VS 11.06 ± 1.03%, P < .05) cells increased significantly, and cell cycle was arrested in S phase. On the other hand, migration detection found the migration of cells also was hindered when lncOGFRP1 level was reduced. And the depletion of lncOGFRP1 inhibited the expression of ß-catenin, Vimentin, N-cadherin, and SNAIL and promoted the expression of E-cadherin. In summary, we first discovered the high expression of lncOGFRP1 in cervical cancer and revealed that silencing lncOGFRP1 inhibits the proliferation and migration of cervical carcinoma cells. SIGNIFICANCE OF THE STUDY: We first discovered the high expression of lncOGFRP1 in cervical cancer and revealed that silencing lncOGFRP1 inhibits the proliferation and migration of cervical carcinoma cells. These results help to better understand the pathogenesis and development of cervical cancer and provide insight to develop better diagnosis and treatment strategies.


Assuntos
Interferência de RNA , RNA Longo não Codificante/metabolismo , Neoplasias do Colo do Útero/patologia , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Humanos , Prognóstico , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Taxa de Sobrevida , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/mortalidade
18.
Gynecol Oncol ; 155(2): 324-330, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31477280

RESUMO

OBJECTIVE: To date, The Cancer Genome Atlas (TCGA) has provided the most extensive molecular characterization of invasive cervical cancer (ICC). Analysis of reverse phase protein array (RPPA) data from TCGA samples showed that cervical cancers could be stratified into 3 clusters exhibiting significant differences in survival outcome: hormone, EMT, and PI3K/AKT. The goals of the current study were to: 1) validate the TCGA RPPA results in an independent cohort of ICC patients and 2) to develop and validate an algorithm encompassing a small antibody set for clinical utility. METHODS: Subjects consisted of 2 ICC patient cohorts with accompanying RPPA and clinical-pathologic data: 155 samples from TCGA (TCGA-155) and 61 additional, unique samples (MCW-61). Using data from 173 common RPPA antibodies, we replicated Silhouette clustering analysis in both ICC cohorts. Further, an index score for each patient was calculated from the survival-associated antibodies (SAAs) identified using Random survival forests (RSF) and the Cox proportional hazard regression model. Kaplan-Meier survival analysis and the log-rank test were performed to assess and compare cluster or risk group survival outcome. RESULTS: In addition to validating the prognostic ability of the proteomic clusters reported by TCGA, we developed an algorithm based on 22 unique antibodies (SAAs) that stratified women with ICC into low-, medium-, or high-risk survival groups. CONCLUSIONS: We provide a signature of 22 antibodies which accurately predicted survival outcome in 2 separate groups of ICC patients. Future studies examining these candidate biomarkers in additional ICC cohorts is warranted to fully determine their clinical potential.


Assuntos
Proteômica , Neoplasias do Colo do Útero/mortalidade , Adulto , Anticorpos Antineoplásicos/genética , Anticorpos Antineoplásicos/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fatores de Risco , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia
19.
Gynecol Oncol ; 155(2): 229-236, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31477283

RESUMO

OBJECTIVE: Survival in cervical cancer has improved little over the last decades. We aimed to elucidate primary treatment patterns and survival. METHODS: Population-based study of patients included in the Swedish Quality Registry for Gynecologic Cancer diagnosed 2011-2015. Main outcome was 5-year relative survival (RS). Age-standardised RS (AS-RS) was estimated for the total cohort and for the pooled study population of squamous, adenosquamous-, adenocarcinoma. RESULTS: Median follow-up time was 4.6 years. The study population consisted of 2141 patients; 97% of the 2212 patients in the total cohort and the 5-year AS-RS was 71% and 70%, respectively. RS stage IB1: surgery alone 95% vs. 72% for definitive chemoradiotherapy (CT-RT) (p < 0.001). In stage IIA1 74% had CT-RT, and 47% of operated patients received adjuvant (CT)-RT. RS stage IB2: surgically treated 81% (69% received adjuvant (CT)-RT) vs. 76% for (CT)-RT (p = 0.73). RS stage IIB: 77% for CT-RT + brachytherapy (BT), 37% for RT + BT (p = 0.045) and 27% for RT-BT (p < 0.001). Stages III-IVA; <40% received CT-RT + BT, RS 45% vs. 18% for RT-BT (RR 4.1, p < 0.001). RS stage IVB 7%. CONCLUSION: Primary treatment of cervical cancer in Sweden adhered to evidence-based standard of care. Areas of improvement include optimising treatment for stages III-IVA, and avoiding combining surgery and radiotherapy.


Assuntos
Neoplasias do Colo do Útero/terapia , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/estatística & dados numéricos , Terapia Combinada/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Prospectivos , Sistema de Registros , Suécia/epidemiologia , Neoplasias do Colo do Útero/mortalidade , Adulto Jovem
20.
In Vivo ; 33(5): 1659-1665, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31471420

RESUMO

BACKGROUND/AIM: The aim of this study was to compare the clinical outcomes of patients treated by local radiotherapy or chemotherapy for oligo-recurrent cervical cancer with prior pelvic irradiation. PATIENTS AND METHODS: Forty-one patients who had received pelvic irradiation for cervical cancer developed oligo-recurrent (≤5 lesions) relapses and underwent local radiotherapy (n=22) or systemic chemotherapy (n=19). Overall survival (OS), local recurrence-free survival (LRFS) and distant-free survival (DFS) were estimated, and risk factors were identified. RESULTS: The median follow-up was 24.1 months. The group of local radiotherapy showed a significantly superior LRFS, but inferior DFS. There was no significant difference in OS. Multivariate analysis revealed that FIGO stage at initial diagnosis was associated with OS. For patients with early FIGO stages (IB-IIB), local radiotherapy provided a tendency toward longer OS than chemotherapy. CONCLUSION: Out-field oligo-recurrence in patients with initial early FIGO stages may be an indication of salvage radiotherapy.


Assuntos
Pelve/patologia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Imagem Multimodal , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade
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