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1.
Bull Cancer ; 107(3): 385-390, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115180

RESUMO

The group of rare malignant ovarian tumors includes the group of germ cell tumors, sex cords stromal ovarian tumors, small cell carcinoma, malignant Brenner tumors, rare epithelial tumors such as mucinous carcinoma, clear cell carcinoma, or low-grade serous carcinoma, as well as ovarian carcinosarcoma. Together they comprise about 10% of all ovarian tumors. Due to their low prevalence and their heterogeneity, data and treatment recommendations are limited. Even though all ovarian tumors are staged according to the FIGO staging of epithelial ovarian tumors, treatment differs especially in germ cell tumors and sex cords stromal ovarian tumors. Non-epithelial ovarian tumors can arise from a variety of ovarian precursor cells such as germ cells, granulosa cells, theca cells, or stromal fibroblasts. As can be expected already due to their divergent precursor lesions, these malignancies are substantially different but united by their rarity. This overview article gives a comprehensive summary on the pathology and clinical presentation, as well as therapy recommendations of a selection of those rare ovarian tumors, based on the latest national guidelines and related important publications.


Assuntos
Neoplasias Ovarianas , Doenças Raras , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Tumor de Brenner/patologia , Tumor de Brenner/terapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/terapia , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Feminino , Humanos , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Doenças Raras/patologia , Doenças Raras/terapia , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/terapia
2.
Int J Cancer ; 146(7): 1851-1861, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603993

RESUMO

The goal of our study was to demonstrate the spectrum of genomic alterations present in the residual disease of patients with advanced high-grade serous ovarian cancer (HGSOC) after neoadjuvant chemotherapy (NAC), including matched pretreatment biopsies. During the study period between 2006 and 2017, we collected pre-NAC and post-NAC tumor tissue samples from patients with advanced HGSOC. We performed combined next-generation sequencing and immunohistochemistry to identify actionable targets and pathway activation in post-NAC residual tumors. We also examined whether post-NAC profiling of residual HGSOC identified targetable molecular lesions in the chemotherapy-resistant component of tumors. Among 102 post-NAC samples, 41 (40%) of patients had mutations in homologous recombination repair (HRR) genes (HRR deficiency). Patients with HRR mutations had higher tumor mutation burdens (p < 0.001) and higher alterations in the PI3K-AKT-mTOR pathway (p = 0.004) than patients without these HRR mutations. Nevertheless, we found no significant differences in progression-free survival (p = 0.662) and overall survival (OS; p = 0.828) between the two groups. Most patients (91%) had alterations in at least one of the targetable pathways, and those patients with cell cycle (p = 0.004) and PI3K-AKT-mTOR signaling (p = 0.005) pathway alterations had poorer OS (Bonferroni-corrected threshold = 0.0083, 0.05/6). We showed the genomic landscape of tumor cells remaining in advanced HGSOC after NAC. Once validated, these data can help inform biomarker-driven adjuvant studies in targeting residual tumors to improve the outcomes of patients with advanced HGSOC after NAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Cistadenocarcinoma Seroso/genética , Neoplasias Ovarianas/genética , Ovário/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Ciclo Celular/genética , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Genômica , Humanos , Pessoa de Meia-Idade , Mutação/efeitos dos fármacos , Terapia Neoadjuvante/métodos , Neoplasia Residual , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Ovariectomia/métodos , Ovário/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Análise de Sobrevida , Serina-Treonina Quinases TOR/metabolismo
3.
Cancer Immunol Immunother ; 68(11): 1747-1757, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31602489

RESUMO

BACKGROUND: Immunotherapy has become a powerful treatment option for several solid tumor types. The presence of tumor-infiltrating lymphocytes (TIL) is correlated with better prognosis in ovarian cancer, pointing at the possibility to benefit from harnessing their anti-tumor activity. This preclinical study explores the feasibility of adoptive cell therapy (ACT) with TIL using an improved culture method. METHODS: TIL from high-grade serous ovarian cancer were cultured using a combination of IL-2 with agonistic antibodies targeting 4-1BB and CD3. The cells were phenotyped using flow cytometry in the fresh tissue and after expansion. Tumor reactivity was assessed against HLA-matched ovarian cancer cell lines via IFN-γ ELISPOT. RESULTS: Ovarian cancer is highly infiltrated with CD8+ TIL that are preferentially and robustly expanded with the addition of the agonistic antibodies. With a 95% success rate, the TIL are grown to ≥ 100 × 106 cells in 2-3 weeks without over differentiation. In addition, the CD8+ TIL grown with this method showed HLA-restricted tumor recognition. CONCLUSIONS: These results indicate the viability of TIL ACT for refractory ovarian cancer by allowing for the large expansion of anti-tumor TIL in a short time and consistent manner.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Quimiorradioterapia , Cistadenocarcinoma Seroso/terapia , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Neoplasias Ovarianas/terapia , Terapia de Salvação , Cistadenocarcinoma Seroso/imunologia , Cistadenocarcinoma Seroso/secundário , Citotoxicidade Imunológica/imunologia , Feminino , Seguimentos , Humanos , Ativação Linfocitária , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/patologia , Prognóstico
4.
J Surg Oncol ; 120(7): 1208-1219, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31531879

RESUMO

BACKGROUND: Whether patients with advanced tubo-ovarian high-grade serous cancer (HGSC) fare better after upfront debulking surgery (UDS) or neoadjuvant chemotherapy with interval debulking surgery (NACT-IDS) remains controversial. METHODS: We studied patients with HGSC who underwent UDS or NACT-IDS between July 2000 and December 2015, with peritonectomy procedures combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Clinical reports were included peritoneal cancer index (PCI), NACT responses, surgical complexity score (SCS), completeness of cytoreduction (CC), complete follow-up with timing, site, and treatment of recurrence. Outcome measures were morbidity, progression-free survival (PFS), PFS2, and overall survival during a mean 5-year follow-up. RESULTS: A total of 34 patients (23.6%) underwent UDS and 110 (76.4%) NACT-IDS both combined with HIPEC. At a median 66.3-month follow-up, patients who underwent UDS or NACT-IDS had similar outcomes. NACT subgroup responses correlated with PCI, SCS, morbidity, and CC. Patients who underwent UDS had lower recurrence rates than those who responded partly or poorly to NACT (PFS, P < .04; PFS2, P < .01). Despite HIPEC, the peritoneal disease recurred in 42.5% of the overall patients. CONCLUSION: In patients with primary HGSC who undergo UDS or NACT-IDS, despite similar outcomes, peritonectomy procedures combined with HIPEC seem unable to prevent peritoneal recurrence.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/mortalidade , Procedimentos Cirúrgicos de Citorredução/mortalidade , Hipertermia Induzida/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/mortalidade , Peritônio/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adenocarcinoma/terapia , Quimioterapia Adjuvante , Terapia Combinada , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Cistadenocarcinoma Seroso/terapia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Ovarianas/terapia , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/cirurgia , Neoplasias Peritoneais/terapia , Estudos Retrospectivos , Taxa de Sobrevida
5.
BMC Cancer ; 19(1): 748, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362708

RESUMO

BACKGROUND: Primary retroperitoneal serous adenocarcinoma (PRSA) is an extremely uncommon malignancy exclusively reported in females. Due to the rarity of the disease, it is difficult to establish a standardized treatment. CASE PRESENTATION: We describe a unique case of PRSA in a 71-year-old male who presented with right-sided lower back pain and numbness. Magnetic resonance imaging identified a mass invading the adjacent psoas muscle and twelfth rib. Tissue biopsy confirmed poorly differentiated PRSA. Patient was initially treated with neoadjuvant carboplatin and paclitaxel chemotherapy regimen. This resulted in complete radiological resolution of the tumor. However, 12 weeks later, rapid recurrence was noted on follow-up CT scan. The patient was then treated with external radiotherapy with concurrent nivolumab, an anti-PD-1 antibody. The patient displayed a positive response to treatment with reduction in primary tumor and metastases and had a sustained disease control. CONCLUSION: Treatment with radiotherapy in combination with anti-PD-1 antibody could be an effective modality of management for PRSA.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/terapia , Imunoterapia/métodos , Nivolumabe/uso terapêutico , Neoplasias Retroperitoneais/radioterapia , Neoplasias Retroperitoneais/terapia , Idoso , Antineoplásicos Imunológicos/farmacologia , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/efeitos adversos , Carboplatina/uso terapêutico , Cistadenocarcinoma Seroso/diagnóstico por imagem , Seguimentos , Humanos , Fatores Imunológicos/uso terapêutico , Imagem por Ressonância Magnética , Masculino , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Nivolumabe/farmacologia , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Neoplasias Retroperitoneais/diagnóstico por imagem , Resultado do Tratamento
6.
Medicine (Baltimore) ; 98(29): e16433, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335697

RESUMO

RATIONALE: Endometrial neuroendocrine carcinoma is a rare histological subtype of endometrial cancer, divided into low-grade neuroendocrine carcinoma (carcinoid) and high-grade neuroendocrine carcinoma (small cell and large cell neuroendocrine carcinoma). It is characterized by high invasiveness and poor prognosis. L/SCNEC is an extremely rare pathological type of endometrial carcinoma, and the number of reports on this condition is few globally. PATIENT CONCERNS: A 54-year-old Chinese female presented with vaginal bleeding. DIAGNOSES: Outpatient hysteroscopy and endometrial biopsy were performed, and the pathological examination revealed that cervix was invaded by endometrial malignancy. The patient underwent a laparoscopic radical hysterectomy was diagnosed with the mixed large and small cell neuroendocrine carcinoma (L/SCNEC) of the endometrium combined with serous carcinoma III C2 (FIGO2009). INTERVENTIONS: Chemotherapy-radiotherapy-chemotherapy "sandwich" treatment was performed as postoperative therapy. OUTCOMES: After three chemotherapy circles, the patient showed no evidence of further disease progression. LESSONS: L/SCNEC is a rare and invasive disease. Once diagnosed, comprehensive treatments including surgery, radiotherapy, and chemotherapy can prolong the survival of patients and improve the prognosis.


Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Quimioterapia Adjuvante/métodos , Cistadenocarcinoma Seroso , Neoplasias do Endométrio , Endométrio/patologia , Histerectomia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biópsia/métodos , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/fisiopatologia , Carcinoma Neuroendócrino/terapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/fisiopatologia , Carcinoma de Células Pequenas/terapia , Terapia Combinada , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/fisiopatologia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/fisiopatologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Invasividade Neoplásica , Estadiamento de Neoplasias , Resultado do Tratamento , Hemorragia Uterina/diagnóstico , Hemorragia Uterina/etiologia
7.
Future Oncol ; 15(16): 1863-1871, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31140312

RESUMO

Aim: The aim of this study was to reveal the diagnostic and prognostic significance of serum CD26 level in high-grade serous ovarian carcinoma women in China. Methods: There were 229 high-grade serous ovarian carcinoma women and 365 controls. Baseline serum CD26 level was measured using ELISA. A 36-month post-operation follow-up was performed. Results: Baseline serum CD26 level ≤601.5 pg/ml was associated with the increased risk of ovarian carcinoma (OR: 1.67; 95% CI: 1.20-2.32). Baseline serum level of CD26 ≤589.7 pg/ml was related to the elevated risk of cancer death (HR: 1.33; 95% CI: 1.04-1.69). Conclusion: Baseline serum CD26 level might be an independent diagnostic and prognostic marker for high-grade serous ovarian carcinoma.


Assuntos
Biomarcadores Tumorais , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/diagnóstico , Dipeptidil Peptidase 4/sangue , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Terapia Combinada , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Prognóstico , Curva ROC
8.
BMC Cancer ; 19(1): 341, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971221

RESUMO

BACKGROUND: Outcomes of patients with ovarian high-grade serous carcinoma (HGSC) treated with neoadjuvant chemotherapy (NAC) have been widely studied, but there is limited information on the outcomes of patients with non-HGSC. This study aimed to evaluate the outcomes of NAC in non-HGSC patients with advanced-stage ovarian cancer. METHODS: We conducted a retrospective cohort study of patients who underwent NAC for advanced stage non-HGSC between 2002 and 2017 in 17 institutions. Demographics, surgical outcomes, and survival rates were evaluated according to histological subtypes. RESULTS: A total of 154 patients were included in this study, comprising 20 cases (13.0%) of mucinous adenocarcinoma, 31 cases (20.1%) of endometrioid adenocarcinoma, 28 (18.2%) cases of clear cell carcinoma, 29 (18.8%) cases of low-grade serous carcinoma and 12 cases (7.8%) of carcinosarcoma. Complete remission/partial remission after the third cycle of NAC was achieved in 100 (64.9%) patients and optimal debulking surgery (residual disease ≤1 cm) at interval debulking surgery was achieved in 103 (66.9%) patients. The most common reason for performing NAC was high tumor burden (n = 106, 68.8%). The median progression-free survival (PFS) was 14.3 months and median overall survival (OS) was 52.9 months. In multivariate analyses, mucinous and clear cell carcinoma were negative prognostic factors for both PFS (p = 0.007 and p = 0.017, respectively) and OS (p = 0.002 and p = 0.013, respectively). CONCLUSIONS: In this study, poor survival outcomes were observed in patients with mucinous and clear cell carcinoma undergoing NAC. Different treatment strategies are urgently required to improve survival outcomes for this disease subset.


Assuntos
Cistadenocarcinoma Seroso/epidemiologia , Neoplasias Ovarianas/epidemiologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/diagnóstico , Cistadenocarcinoma Seroso/terapia , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/terapia , República da Coreia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
9.
Rev Bras Ginecol Obstet ; 41(4): 264-267, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30991420

RESUMO

BACKGROUND: Most endometrial cancers (75%) are diagnosed in early stages (stages I and II), in which abnormal uterine bleeding is the most frequent clinical sign. When the diagnosis is performed in stage IV, the most common sites of metastasis are the lungs, liver and bones. Central nervous system (CNS) metastasis is a rare condition. The aim of this study is to describe a case of uterine papillary serous adenocarcinoma of the endometrium that progressed to brain and bone metastases. CASE REPORT: We present the case of a 56-year-old woman with abnormal uterine bleeding and endometrial thickened echo (1.8 cm). A hysteroscopy with biopsy was performed, which identified poor differentiated serous adenocarcinoma of the endometrium. A total abdominal hysterectomy, with pelvic and para-aortic lymphadenectomy, was performed. Analysis of the surgical specimen revealed a grade III uterine papillary serous adenocarcinoma. Adjuvant radio/chemotherapy (carboplatin and paclitaxel-six cycles) was indicated. Sixteen months after the surgery, the patient began to complain of headaches. Brain magnetic resonance imaging demonstrated an expansile mass in the right parietal lobe, suggesting a secondary hematogenous implant subsequently confirmed by biopsy. She underwent surgery for treatment of brain metastasis, followed by radiotherapy. She died 12 months after the brain metastasis diagnosis due to disease progression. CONCLUSION: Uterine papillary serous adenocarcinoma of the endometrium has a low propensity to metastasize to the brain. To the best of our knowledge, this is the fifth documented case of uterine papillary serous adenocarcinoma of the endometrium with metastasis to the CNS.


Assuntos
Neoplasias Encefálicas/diagnóstico , Cistadenocarcinoma Seroso/diagnóstico , Neoplasias do Endométrio/diagnóstico , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/terapia , Terapia Combinada , Cistadenocarcinoma Seroso/complicações , Cistadenocarcinoma Seroso/secundário , Cistadenocarcinoma Seroso/terapia , Diagnóstico Diferencial , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Evolução Fatal , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Hemorragia Uterina/etiologia
10.
Int J Mol Sci ; 20(4)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30813239

RESUMO

Among a litany of malignancies affecting the female reproductive tract, that of the ovary is the most frequently fatal. Moreover, while the steady pace of scientific discovery has fuelled recent ameliorations in the outcomes of many other cancers, the rates of mortality for ovarian cancer have been stagnant since around 1980. Yet despite the grim outlook, progress is being made towards better understanding the fundamental biology of this disease and how its biology in turn influences clinical behaviour. It has long been evident that ovarian cancer is not a unitary disease but rather a multiplicity of distinct malignancies that share a common anatomical site upon presentation. Of these, the high-grade serous subtype predominates in the clinical setting and is responsible for a disproportionate share of the fatalities from all forms of ovarian cancer. This review aims to provide a detailed overview of the clinical-pathological features of ovarian cancer with a particular focus on the high-grade serous subtype. Along with a description of the relevant clinical aspects of this disease, including novel trends in treatment strategies, this text will inform the reader of recent updates to the scientific literature regarding the origin, aetiology and molecular-genetic basis of high-grade serous ovarian cancer (HGSOC).


Assuntos
Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Animais , Biomarcadores Tumorais/metabolismo , Cistadenocarcinoma Seroso/classificação , Cistadenocarcinoma Seroso/epidemiologia , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Gradação de Tumores , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/epidemiologia , Fatores de Risco
11.
J Gynecol Oncol ; 30(3): e32, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30887755

RESUMO

OBJECTIVE: Somatic TP53 mutation (TP53mut) is a characteristic finding in high-grade serous ovarian cancer (HGSOC). The aim of this study was to assess the clinical efficacy and utility of TP53mut circulating tumor DNA (ctDNA) monitoring as a biomarker for managing HGSOC. METHODS: TP53muts were evaluated in patients who received primary treatment for suspected ovarian cancer at Asan Medical Center. In patients diagnosed with HGSOC and with TP53mut, ctDNA, cancer antigen 125 (CA 125), and computed tomography were followed up according to the treatment course. RESULTS: Direct sequencing analysis of 103 tumor tissues from 61 HGSOC patients confirmed TP53muts in 41 patients (67.2%). All these patient-specific somatic mutations were detected in plasma cell-free DNA. The mean value of preoperative TP53 mutant allele count (TP53MAC) in stage III patients was 12.2 copies/µL and in stage IV patients was 45.3 copies/µL. TP53MAC was significantly reduced by treatment and there was no significant difference in the rate of decrease compared to CA 125 by the generalized linear mixed model. When patients were divided into a low TP53MAC group (<0.2 copies/µL) and a high TP53MAC group (≥0.2 copies/µL) based on the TP53MAC value at 3 months after the end of chemotherapy, there was a significant difference in time to progression between the two groups (p=0.038). CONCLUSION: TP53mut ctDNA shows potential as a tumor-specific biomarker for treatment response monitoring in HGSOC. TP53mut ctDNA levels at 3 months post treatment has a significant prognostic utility than that of CA 125.


Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Cistadenocarcinoma Seroso/diagnóstico , Análise Mutacional de DNA , Monitorização Fisiológica/métodos , Neoplasias Ovarianas/diagnóstico , Proteína Supressora de Tumor p53/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Antígeno Ca-125/análise , Antígeno Ca-125/sangue , Quimioterapia Adjuvante , DNA Tumoral Circulante/análise , DNA Tumoral Circulante/sangue , Terapia Combinada , Cistadenocarcinoma Seroso/sangue , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/terapia , Ovariectomia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Proteína Supressora de Tumor p53/análise , Proteína Supressora de Tumor p53/sangue
12.
J Gynecol Oncol ; 30(3): e44, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30887761

RESUMO

OBJECTIVE: To compare the survival outcomes of adjuvant radiotherapy and chemotherapy in women with uterine-confined endometrial cancer with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CCC). METHODS: Medical records of 80 women who underwent surgical staging for endometrial cancer were retrospectively reviewed. Stage I UPSC and CCC were pathologically confirmed after surgery. Survival outcomes were compared between the adjuvant radiotherapy and chemotherapy groups. RESULTS: Fifty-four (67.5%) and 26 (32.5%) women had UPSC and CCC, respectively. Adjuvant therapy was administered to 59/80 (73.8%) women (25 radiotherapy and 34 chemotherapy). High preoperative serum cancer antigen-125 level (25.1±20.2 vs. 11.5±6.5 IU/mL, p<0.001), open surgery (71.2% vs. 28.6%, p=0.001), myometrial invasion (MI) ≥1/2 (33.9% vs. 0, p=0.002), and lymphovascular space invasion (LVSI; 28.8% vs. 4.8%, p=0.023) were frequent in women who received adjuvant therapy compared to those who did not. However, the histologic type, MI ≥1/2, and LVSI did not differ between women who received adjuvant radiotherapy and those who received chemotherapy. The 5-year progression-free survival (78.9% vs. 80.1%, p>0.999) and overall survival (77.5% vs. 87.8%, p=0.373) rates were similar between the groups. Neither radiotherapy (hazard ratio [HR]=1.810; 95% confidence interval [CI]=0.297-11.027; p=0.520) nor chemotherapy (HR=1.638; 95% CI=0.288-9.321; p=0.578) after surgery was independently associated with disease recurrence. CONCLUSION: Our findings showed similar survival outcomes for adjuvant radiotherapy and chemotherapy in stage I UPSC and CCC of the endometrium. Further large study with analysis stratified by MI or LVSI is required.


Assuntos
Adenocarcinoma de Células Claras , Quimioterapia Adjuvante/mortalidade , Cistadenocarcinoma , Neoplasias do Endométrio , Radioterapia Adjuvante/mortalidade , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada/mortalidade , Cistadenocarcinoma/mortalidade , Cistadenocarcinoma/patologia , Cistadenocarcinoma/terapia , Cistadenocarcinoma Papilar/mortalidade , Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Papilar/terapia , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Humanos , Histerectomia/mortalidade , Pessoa de Meia-Idade , Estadiamento de Neoplasias , República da Coreia/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
13.
Int J Gynecol Cancer ; 29(1): 133-139, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640695

RESUMO

OBJECTIVE: High grade and non-endometrioid endometrial cancers carry a poor prognosis, and the lack of randomized prospective data has led to a wide range of practice regarding adjuvant therapy. The objective of this study was to evaluate the outcomes of different treatment strategies in patients with high-risk, early-stage endometrial cancer. METHODS: Patients with high-grade endometrioid, serous endometrial cancer and carcinosarcoma diagnosed between 2000 and 2012 were identified from databases in three gynecologic oncology divisions, in Toronto and in Israel. Adjuvant treatment practices differed across the centers, creating a heterogeneous cohort. A comparison of stage I patients stratified by adjuvant treatment was undertaken. Log-rank tests and Cox proportional hazards models were employed to compare recurrence and survival across treatment groups. RESULTS: 490patients with high risk endometrial cancer were identified, among them 213 patients with stage I disease. Israeli patients received more chemotherapy (41% vs 10% in stage I disease; P<0.001) than patients in Toronto. Chemotherapy was not associated with improved disease-free, disease-specific or overall survival, nor was it associated with fewer distant recurrences (50% vs 54%). Radiation was also not associated with improved recurrence or survival, nor did it affect the pattern of recurrence. On Cox multivariable analysis, neither radiation treatment nor chemotherapy were significantly associated with outcome (HR for recurrence, 0.72 for pelvic radiation (P=0.46) and 1.99 for chemotherapy (P=0.09); HR for death, 0.67 for pelvic radiation (P=0.29) and 1.03 for chemotherapy (P=0.94)). CONCLUSIONS: In this retrospective analysis, neither adjuvant radiation nor chemotherapy were associated with improved outcome in stage I, high risk endometrial cancer.


Assuntos
Carcinossarcoma/mortalidade , Quimiorradioterapia Adjuvante/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Neoplasias do Endométrio/mortalidade , Recidiva Local de Neoplasia/mortalidade , Idoso , Carcinossarcoma/patologia , Carcinossarcoma/terapia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/terapia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
14.
Int J Gynecol Cancer ; 29(1): 158-165, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640699

RESUMO

OBJECTIVE: To investigate treatment choices and outcomes in women with ovarian cancer, comparing elderly (≥75 years) and younger patients (<75 years). METHODS: A single-center retrospective analysis of patients diagnosed with ovarian cancer between 2010 and 2015. The initial treatment plan and course of treatment were extracted from medical files. RESULTS: Of 128 included patients, 34% were aged ≥75 years. The initial treatment plan consisted of the combination of cytoreductive surgery and platinum-based doublet chemotherapy (ie, standard treatment) in only 10% of the elderly patients with an indication for this treatment. 5% of these patients completed this treatment without adaptations (compared with 85% and 48%, respectively, in younger patients). 38% of the elderly patients with an indication for cytoreductive surgery and chemotherapy received best supportive care only. Patient preference was an important reason to withhold standard treatment. Surgery- and chemotherapy-related complications and hospital admissions did not differ between groups. Median survival was lower in the elderly (p=0.002) and in patients receiving best supportive care (p<0.001). CONCLUSIONS: Elderly patients were less frequently treated in accordance with the treatment guideline. To select those older patients who may benefit from (adapted) treatment is challenging. Future studies should evaluate determinants associated with treatment completion to improve outcomes in this vulnerable population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Tomada de Decisões , Neoplasias Ovarianas/terapia , Qualidade de Vida , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Terapia Combinada , Cistadenocarcinoma Seroso/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
15.
Int J Gynecol Cancer ; 29(1): 174-180, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30640701

RESUMO

OBJECTIVES: Low grade serous ovarian carcinoma is a rare subtype of ovarian cancer with an indolent and chemorefractory course. As such, treatment strategies among practitioners are not uniformly known. The primary objective of this study was to identify differences in practice patterns among physicians who treat low grade serous carcinoma. METHODS MATERIALS: A de novo survey was distributed to members of the Society of Gynecologic Oncology. Questions about demographics, management of primary and recurrent disease, and use of consolidation therapy were included. Statistical analyses were performed using χ2 and Fisher's exact tests. RESULTS: 194 gynecologic oncologists completed the survey. Approximately two-thirds of respondents practiced in a university based setting and treated a high volume of ovarian cancers, including low grade serous carcinoma. 82% recommended somatic testing during treatment and 84% routinely sent patients for genetic counseling. Treatment preferences for primary disease varied by debulking status. 48% of practitioners used hormone antagonism as consolidation after primary treatment. Secondary cytoreduction was preferred for patients with platinum sensitive recurrence and a long disease free interval following primary treatment (P<0.001). Hormone antagonism was the preferred treatment for the first platinum resistant recurrence (54%), while a BRAF inhibitor was the preferred agent in platinum resistant recurrence in the presence of a known BRAF mutation (56%). CONCLUSIONS: There was significant variation in the preferred management of low grade serous carcinoma among practitioners. Further efforts to improve knowledge of this disease, identify optimal treatment modalities, and provide guidelines for management should be encouraged.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias Ovarianas/terapia , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/normas , Terapia Combinada , Cistadenocarcinoma Seroso/patologia , Feminino , Preservação da Fertilidade , Seguimentos , Humanos , Gradação de Tumores , Recidiva Local de Neoplasia/patologia , Tratamentos com Preservação do Órgão , Neoplasias Ovarianas/patologia
16.
J Gynecol Oncol ; 30(1): e3, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30479087

RESUMO

OBJECTIVES: We conducted a protocol-based cohort study to evaluate the outcomes of interval debulking surgery (IDS) followed by paclitaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of advanced-stage ovarian cancer. METHODS: From October 2015 to May 2018, 65 patients with stages IIIC-IV ovarian cancer were treated according to the study protocol. HIPEC was performed with paclitaxel (175 mg/m²) for 90 minutes, only in cases of optimal cytoreduction. RESULTS: Of 65 patients, 40 (61.5%) patients underwent neoadjuvant chemotherapy (NAC), 34 (52.3%) patients had a high tumor burden with a Fagotti score ≥8 at diagnostic laparoscopy, and 6 (9.2%) had definite stage IV metastasis and/or poor performance status before NAC. Twenty-seven (41.5%) patients underwent IDS followed by HIPEC. The mean duration of IDS with HIPEC was 543.8 (range, 277.0-915.0) minutes. Grade III/IV perioperative complications occurred in 7.4% (n=2)/3.7% (n=1) of patients and no cases of mortality were reported within 30 days postoperatively. The median progression-free survival was 21.3 months, and the median overall survival was not reached for those who received HIPEC. CONCLUSIONS: According to our study protocol, IDS followed by paclitaxel-based HIPEC as a first-line treatment appears to be feasible and safe for the treatment of advanced-stage ovarian cancer. Further evaluations of this procedure are required to assess its survival benefits.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Cistadenocarcinoma Seroso/terapia , Hipertermia Induzida/métodos , Neoplasias Ovarianas/terapia , Paclitaxel/administração & dosagem , Adulto , Idoso , Antineoplásicos Fitogênicos/efeitos adversos , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/efeitos adversos , Projetos Piloto , Intervalo Livre de Progressão
17.
J Gynecol Oncol ; 30(1): e11, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30479095

RESUMO

OBJECTIVE: Elderly age is one of the poor prognostic factors in epithelial ovarian cancer (EOC), but the optimal age cut-off is not known. The present study sought to identify the ideal age cutoff that represents a negative prognostic factor in EOC, considering the geriatric assessment. METHODS: Hazard ratios (HRs) with p-values were calculated using all possible age cutoffs with stage, histology, grade, optimality and comorbidities as covariates in multivariate Cox regression model. The trends of p-value and HR by age cutoff were further evaluated in a subgroup of histology and in The Cancer Genome Atlas (TCGA) dataset. In addition, propensity score-matching analysis using the identified age cutoff was performed. RESULTS: An age of 66 years was shown to be the most significant cutoff for defining old age with independent prognostic power (HR=1.45; 95% confidence interval=1.04-2.03; p=0.027). This result was also observed with the analyses of serous histology subgroup and with the analysis of a TCGA dataset with serous EOC. In survival analysis, patients aged ≥66 years had significantly worse overall survival compared with younger individuals (56 months vs. 87 months; p=0.006), even following propensity score matching (57 vs. 78 months; p=0.038). CONCLUSION: An age of 66 years is the best cutoff to define elderly age in serous EOC patients considering the geriatric assessment, and this information can be used in the administration of individualized therapies in elderly EOC patients.


Assuntos
Fatores Etários , Carcinoma Epitelial do Ovário/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Neoplasias Ovarianas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/terapia , Cistadenocarcinoma Seroso/terapia , Feminino , Avaliação Geriátrica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neoplasias Ovarianas/terapia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida
18.
Cancer Epidemiol ; 58: 77-82, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30528360

RESUMO

BACKGROUND: Black women with ovarian cancer in the U.S. have lower survival than whites. We aimed to identify factors associated with racial differences in ovarian cancer treatment and overall survival (OS). METHODS: We examined data from 365 white and 95 black ovarian cancer patients from the Hollings Cancer Center Cancer Registry in Charleston, S.C. between 2000 and 2015. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between race and receipt of surgery and chemotherapy, and Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs between race and OS. Model variables included diagnosis center, stage, histology, insurance status, smoking, age-adjusted Charlson comorbidity index (AACI) and residual disease. Interactions between race and AACI were assessed using -2 log likelihood tests. RESULTS: Blacks vs. whites were over two-fold less likely to receive a surgery-chemotherapy sequence (multivariable-adjusted OR 2.46, 95% CI 1.43-4.21), particularly if they had a higher AACI (interaction p = 0.008). In multivariable-adjusted Cox models, black women were at higher risk of death (HR 1.81, 95% CI 1.35-2.43) than whites, even when restricted to patients who received a surgery-chemotherapy sequence (HR 1.79, 95% CI 1.10-2.89) and particularly for those with higher AACI (HR 4.70, 95% CI 2.00 - 11.02, interaction p = 0.01). CONCLUSIONS: Among blacks, higher comorbidity associates with less chance of receiving guideline-based treatment and also modifies OS. Differences in receipt of guideline-based care do not completely explain survival differences between blacks and whites with ovarian cancer. These results highlight opportunities for further research.


Assuntos
Afro-Americanos/estatística & dados numéricos , Grupo com Ancestrais do Continente Europeu/estatística & dados numéricos , Disparidades em Assistência à Saúde , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Terapia Combinada , Comorbidade , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida
19.
Brachytherapy ; 18(1): 38-43, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30316723

RESUMO

PURPOSE: The treatment paradigm for uterine clear cell carcinoma is often linked to serous carcinoma. This study compares oncologic outcomes between women with uterine clear cell and serous carcinoma. METHODS AND MATERIALS: We reviewed 114 women with stage I-II uterine clear cell carcinoma (n = 17, 15%) or serous carcinoma (n = 97, 85%) who underwent hysterectomy and salpingo-oophorectomy at our institution from April 1992 to December 2011; 86 (76%) had stage IA, 14 (12%) had stage IB, and 14 (12%) had stage II disease. Median followup was 57 months. RESULTS: Patients with uterine clear cell and serous carcinoma did not differ significantly by age ≥60 years, stage, or rate of lymphovascular invasion. There was no difference in the number of patients with clear cell or serous histology who received adjuvant radiotherapy (71% vs. 84%, respectively; p = 0.31); however, significantly fewer patients with clear cell histology received adjuvant chemotherapy (35% vs. 67%, respectively; p = 0.02). At 5 years, there were no significant differences in disease-free survival (94% vs. 84%, respectively; p = 0.27), disease-specific survival (100% vs. 92%, respectively; p = 0.20), or overall survival (100% vs. 89%, respectively; p = 0.34). The differences in chemotherapy utilization did not impact pattern of relapse, specifically peritoneal spread (7% vs. 6%, respectively; p = 0.92) or other distant sites (0% vs. 9%, respectively; p = 0.17). CONCLUSIONS: Oncologic outcomes and recurrence patterns of women with stage I-II uterine clear cell carcinoma compared favorably with those of women with serous carcinoma, despite significantly less adjuvant chemotherapy use. Potential reduction in adjuvant therapy in women with clear cell carcinoma should be studied prospectively.


Assuntos
Adenocarcinoma de Células Claras/terapia , Cistadenocarcinoma Seroso/terapia , Neoplasias Uterinas/terapia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia , Quimioterapia Adjuvante , Terapia Combinada , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Intervalo Livre de Doença , Feminino , Humanos , Histerectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Ovariectomia , Radioterapia Adjuvante , Estudos Retrospectivos , Salpingectomia , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia
20.
Gynecol Oncol ; 152(2): 228-234, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30471899

RESUMO

OBJECTIVE: It is unclear if the types of surgical procedures performed on long-term survivors (LTS) of high-grade serous ovarian carcinoma (HGSOC) contribute to prolonged survival. In this case-control study we review the surgical procedures performed on LTS and describe their individual longitudinal disease courses. METHODS: Women with FIGO stage III-IV high-grade serous cancer of the ovary, fallopian tube or peritoneum were selected from the University of Chicago ovarian cancer database. LTS were those surviving >7 years and controls were short-term survivors (STS) living 1-2 years. Patients with non-serous histology, low grade, and low malignant potential tumors were excluded. RESULTS: We identified 450 women with stage III/IV HGSOC including 45 LTS and 78 STS. LTS showed a trend towards lower disease burden, yet underwent more aggressive surgical treatment. Interestingly, only 15 LTS (34%) were debulked to microscopic disease and 9 LTS (21%) underwent suboptimal debulking. Two LTS (5%) recurred within 12 months. LTS had heterogeneous clinical courses with 13 (29%) never experiencing a recurrence with 143 months median follow-up and 32 (71%) experiencing a recurrence with 115 months median follow-up. Of the women who recurred, 19 (59%) underwent at least one surgery for recurrence. CONCLUSIONS: Aggressive surgical treatment intended to achieve microscopic disease, primary debulking surgery, preservation of sensitivity to chemotherapy, and recurrence amenable to secondary debulking are associated with long-term survival. However, clinicopathologic data are insufficient to predict long-term survival of HGSOC. Biologic characterization of these patient's tumors likely holds the key to understanding their unusually favorable courses.


Assuntos
Sobreviventes de Câncer , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/terapia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/cirurgia , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia
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