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1.
Gynecol Oncol ; 160(1): 77-82, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33059915

RESUMO

OBJECTIVE: In young women, EOC is a rare disease with an uncertain genetic and biological substrate. METHODS: We report a long follow-up of EOC patients treated at Gustave Roussy between 1990 and 2009. We matched young patients aged ≤30 years to randomly selected older patients aged ≥40 years according to known prognostic factors (i.e. FIGO stage, histology and surgical residual disease) and the date of diagnosis with a threshold at the year 2000 to balance the treatment procedures. RESULTS: EOC was diagnosed in 68 patients aged ≤30 years matched with 111 patients aged ≥40 years. Low-grade (LG) (i.e. serous and endometrioid) (52%, n = 35) and mucinous (i.e. 23%, n = 16 infiltrative and 12% n = 8 expansile) tumors are prevalent. High-grade (HG) tumors are rare (7%, n = 5). Early stage diseases (53%, n = 36 FIGO I/II) are predominant. Response to platinum based chemotherapy is observed to be inferior in young patients as compared to matched older patients (ORR, 29 vs 84% p = 0.0002). For HG tumors the PFS is of 0% at 5 and 10 years in younger as compared to 30% in older patients. No difference in PFS (median 4.9 vs 9.8 ms, p = 0.58) and OS (not reached vs 15.3 ms, p = 0.47) is found overall among younger and older patients respectively. The median follow-up was 72 months (range, 11-288 months). No genetic abnormalities were found. CONCLUSIONS: Young EOC patients are most often diagnosed at an early FIGO stage with LG serous or mucinous histology. Tumors are significantly more resistant to platinum-based chemotherapy in younger patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
2.
Oncologist ; 22(2): 182-188, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28174295

RESUMO

PURPOSE: The phase III European Organization for Research and Treatment of Cancer 55874 study has shown that external beam radiotherapy (EBRT) given as adjuvant treatment decreased locoregional recurrences from 40% to 20% in patients (pts) with localized uterine sarcomas (US). No data exist, however, on the place of brachytherapy (BT). MATERIAL AND METHODS: We conducted a single-center retrospective analysis of pts receiving adjuvant BT of the vaginal vault based on the vaginal mold technique as part of their multimodal adjuvant treatment for a high-grade US from 1985 to 2015. Treatment characteristics, patterns of relapse, and toxicity were examined. RESULTS: Median follow-up time was 5.5 years. A total of 98 pts with high-grade US were identified: 81 leiomyosarcomas and 17 undifferentiated sarcomas. Postoperative chemotherapy was delivered in 53 pts. Median dose of EBRT was 45 Gy in 25 fractions. High-dose rate, low-dose rate, and pulsed-dose rate techniques were used in 66, 31, and 1 pts, respectively. At last follow-up, six pts (6.1%) experienced a locoregional relapse as first event. The International Federation of Gynecology and Obstetrics stage and the tumor size were associated with a higher probability of local relapse. When focusing on pts with stage I-III disease, 5-year overall survival was 77% (95% confidence interval: 67%-87%) and 5-year survival without locoregional failure was 91% (83%-98%). Toxicities were mild to moderate, with only four acute grade 3 toxicities and two grade 3 late effects. CONCLUSION: Vaginal vault BT as part of a multimodal adjuvant treatment was associated with a high locoregional control rate and with acceptable side effects in localized high-grade US. The Oncologist 2017;22:182-188Implications for Practice: This study suggests that an aggressive adjuvant treatment combining chemotherapy and pelvic external beam radiotherapy followed with a brachytherapy of the vaginal vault is associated with a high locoregional control rate and an acceptable toxicity rate in patients with high grade uterine sarcoma. Adding a brachytherapy boost could also allow deescalating the total dose of pelvic external beam radiotherapy, in order to decrease the side effects of adjuvant treatment in these patients without increasing the risk of local relapse. However, the prognosis remains determined by a high frequency of systemic relapses.


Assuntos
Braquiterapia/métodos , Quimioterapia Adjuvante/métodos , Sarcoma/cirurgia , Neoplasias do Colo do Útero/cirurgia , Vagina/cirurgia , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Estudos Retrospectivos , Sarcoma/patologia , Análise de Sobrevida , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologia , Adulto Jovem
3.
Gynecol Oncol ; 142(3): 452-7, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27401840

RESUMO

BACKGROUND: The ovarian yolk sac tumor (OYST) is a very rare malignancy arising in young women. Our objective was to determine whether an early decline in serum alpha-fetoprotein (AFP) during chemotherapy has a prognostic impact. METHODS: This retrospective study is based on prospectively recorded OYST cases at Gustave Roussy (Cancer Treatment Center). Survival curves were estimated using the Kaplan-Meier method. The serum AFP decline was calculated with the formula previously developed and validated in male patients with poor prognosis non-seminomatous germ cell tumors. Univariate and multivariate analyses were performed using the log-rank test and logistic regression, respectively. RESULTS: Data on AFP were available to calculate an early AFP decline in 57 patients. All patients had undergone surgery followed by chemotherapy. The 5-year overall survival (OS) and event-free survival (EFS) rates were 86% (95% CI: 74%-93%) and 84% (95% CI: 73%-91%), respectively. The disease stage, presence of ascites at presentation, use of the BEP regimen, serum AFP half-life and an early AFP decline were significantly predictive factors for OS and EFS in the univariate analysis. The OS rate was 100% and 49% (95% CI: 26%-72%) in patients with a favorable AFP decline and in those with an unfavorable decline, respectively (p<0.001). In the multivariate analysis, only the presence of ascites at diagnosis (RR=7.3, p=0.03) and an unfavorable early AFP decline (RR=16.9, p<0.01) were significant negative predictive factors for OS. CONCLUSIONS: An early AFP decline during chemotherapy is an independent prognostic factor in patients with OYSTs. CONFLICT OF INTEREST STATEMENT: No conflict of interest.


Assuntos
Tumor do Seio Endodérmico/sangue , Tumor do Seio Endodérmico/tratamento farmacológico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/tratamento farmacológico , alfa-Fetoproteínas/metabolismo , Adolescente , Adulto , Tumor do Seio Endodérmico/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
4.
Gynecol Oncol ; 143(1): 27-34, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27546885

RESUMO

PURPOSE: Trebananib, a peptibody that blocks binding of angiopoietin-1 and -2 to Tie2, significantly prolonged progression-free survival (PFS) in patients with recurrent epithelial ovarian cancer in the phase 3 TRINOVA-1 study. We report overall survival (OS) in the intent-to-treat population and clinically relevant subgroups and time to second disease progression (PFS-2). PATIENTS AND METHODS: Women with recurrent disease (platinum-free interval<12months) were randomized to receive intravenous paclitaxel 80mg/m(2) (3weeks on/1week off) plus intravenous trebananib 15mg/kg or placebo, weekly. OS in the intent-to-treat population was a key secondary endpoint. Exploratory analysis of PFS-2 was conducted according to guidance by the European Medicines Agency. RESULTS: Median OS was not significantly improved with trebananib compared with placebo (19.3 versus 18.3months; HR, 0.95; 95% CI, 0.81-1.11; P=0.52) in the intent-to-treat population (n=919). In subgroup analysis, trebananib improved median OS compared with placebo (14.5 versus 12.3months; HR, 0.72; 95% CI, 0.55-0.93; P=0.011) in patients with ascites at baseline (n=295). In the intent-to-treat population, trebananib significantly improved median PFS-2 compared with placebo (12.5 versus 10.9months; HR, 0.85; 95% CI, 0.74-0.98; P=0.024). The incidence and type of adverse events in this updated analysis was consistent with that described in the primary analysis; no new safety signals were detected. CONCLUSIONS: OS was not significantly longer in the intent-to-treat population, although there was an improvement in OS in patients with ascites receiving trebananib. PFS-2 confirmed that the PFS benefit associated with trebananib was maintained through the second disease progression independent of the choice of subsequent therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ascite/etiologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/mortalidade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos
5.
Chemotherapy ; 61(1): 15-22, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26528705

RESUMO

BACKGROUND: Dose-intensive chemotherapy with hematopoietic stem cell transplantation has been evaluated as a salvage treatment for recurrent ovarian cancer, but its benefit has not yet been demonstrated. In a previous phase I trial, we reported the feasibility of administering topotecan as a salvage regimen. METHODS: Twenty-one patients were treated with escalating doses of topotecan associated with a fixed dose of cyclophosphamide. RESULTS: The maximum tolerated dose was established at 9.0 mg/m2 on a 5-day regimen, analogously to what was reported for topotecan monotherapy. One toxic death from septic shock and multiorgan failure occurred. Although hematopoietic toxicities were overcome by peripheral blood stem cell transplantation, superior nonhematological toxicities were observed as compared to the initial trial. CONCLUSION: Response rates were generally short and survival rates were poor. Results of the ITOV 01bis study demonstrate that, in the setting of recurrent ovarian cancer, intensive chemotherapy based on topotecan-cyclophosphamide association is not currently clinically indicated.


Assuntos
Adenocarcinoma de Células Claras/terapia , Adenocarcinoma Mucinoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/terapia , Neoplasias do Endométrio/terapia , Transplante de Células-Tronco Hematopoéticas , Neoplasias Ovarianas/terapia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adolescente , Adulto , Idoso , Estudos de Coortes , Terapia Combinada , Ciclofosfamida/administração & dosagem , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Terapia de Salvação , Taxa de Sobrevida , Topotecan/administração & dosagem , Adulto Jovem
6.
Ann Surg Oncol ; 22 Suppl 3: S964-70, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26033179

RESUMO

BACKGROUND: The goal, methods, and results of surgery for growing teratoma syndrome (GTS) in men after testicular cancer have been well described. The main surgical challenge relates to the need for vascular or thoracic procedures. But little is known about GTS in women, particularly regarding the optimal management of intraabdominal disease. This study aimed to evaluate the surgical management and outcomes (recurrences and fertility) for a large series of ovarian GTS. METHODS: This study retrospectively analyzed patients treated for an ovarian immature teratoma (IT) who subsequently experienced abdominal GTS requiring surgery. RESULTS: Between 1983 and 2014, 196 cases of IT were referred to the authors' institution or treated there, and 38 patients (19 %) subsequently experienced a GTS, including 10 cases of gliomatosis peritonei (containing exclusively pure mature glial tissue). The median age at diagnosis was 26 years (range 8-41 years), and the mean delay between IT and GTS diagnosis was 7 months (range 3-84 months). Surgical resection included peritonectomy (n = 22), diaphragmatic peritoneal resection (n = 14), bowel resection (n = 8), and splenectomy (n = 5). Conservative surgery was possible for 20 patients. Complete cytoreductive surgery was achieved for 25 patients. The mean follow-up period was 73 months (range 3-263 months). At least one recurrence developed for 10 patients (in the form of mature disease in all, and 8 of these patients had an initial complete resection. Five patients had a pregnancy. One patient died of complications from the disease (pulmonary embolism in a patient with bowel obstruction). CONCLUSIONS: The overall prognosis of abdominal GTS is good. The surgical procedures for GTS are similar to those used in debulking surgery for epithelial cancer. Whenever technically possible, a conservative surgery should be performed because spontaneous fertility is possible. Recurrent GTS is frequent even after complete surgery.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Ovarianas/cirurgia , Peritônio/cirurgia , Teratoma/cirurgia , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Masculino , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Ovarianas/patologia , Peritônio/patologia , Gravidez , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Teratoma/patologia , Adulto Jovem
7.
Int J Gynecol Cancer ; 25(2): 296-302, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25581897

RESUMO

OBJECTIVE: Uterine leiomyosarcoma (ULMS) is a rare gynecologic malignancy characterized by a poor prognosis due to a high rate of local and metastatic recurrences. Chemotherapy with doxorubicin or ifosfamide or both is associated with a 10% to 30% objective response rate. We report a monocentric experience with doxorubicin, cisplatin, and ifosfamide (API) combination in the setting of multimodal treatment of advanced or metastatic ULMS. PATIENTS AND METHODS: This monocentric retrospective study included patients with metastatic or locally advanced ULMS with a physiological age younger than 65 years treated in first line with a multimodal aggressive approach with API chemotherapy. Treatment consisted of doxorubicin 50 mg/m2 d1, ifosfamide 3 g/m2 per day d1d2 plus mesna, cisplatin 75 mg/m2 d3, plus G-CSF; every 3 weeks up to 6 cycles. Surgery, radiation therapy, or radiofrequency ablation therapy of metastatic sites was associated whenever possible. RESULTS: Thirty-eight patients received API for metastatic or locally advanced ULMS. Median age was 51 years (40-64 years); 4 (11%) patients were treated for a locally advanced disease and 34 (89%) for metastatic disease. Sixteen patients responded (4 complete responses+12 partial responses) among 33 evaluable patients (objective response rate, 48%); 8 and 9 patients had, respectively, stable and progressive disease. Twelve patients had surgeries with 9 surgical complete responses and 3 surgical partial responses. Median progression-free and overall survival in the whole population were 9.8 and 27 months, respectively. Main grade 3-4 toxicities in 38 patients were neutropenia (74%), thrombocytopenia (60%), anemia (55%), fatigue (18%), and vomiting (13%). Febrile neutropenia was observed in 37% of patients. CONCLUSIONS: Despite the toxicity observed, API is an effective treatment which compares favorably with other first-line therapies for patients with metastatic or advanced ULMS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Doxorrubicina/administração & dosagem , Ifosfamida/administração & dosagem , Leiomiossarcoma/tratamento farmacológico , Neoplasias Uterinas/tratamento farmacológico , Adulto , Ablação por Cateter , Cisplatino/efeitos adversos , Terapia Combinada , Progressão da Doença , Doxorrubicina/efeitos adversos , Feminino , Procedimentos Cirúrgicos em Ginecologia , Humanos , Ifosfamida/efeitos adversos , Leiomiossarcoma/mortalidade , Leiomiossarcoma/patologia , Leiomiossarcoma/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias Uterinas/mortalidade , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia
8.
Lancet Oncol ; 15(8): 799-808, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24950985

RESUMO

BACKGROUND: Angiogenesis is a valid target in the treatment of epithelial ovarian cancer. Trebananib inhibits the binding of angiopoietins 1 and 2 to the Tie2 receptor, and thereby inhibits angiogenesis. We aimed to assess whether the addition of trebananib to single-agent weekly paclitaxel in patients with recurrent epithelial ovarian cancer improved progression-free survival. METHODS: For this randomised, double-blind phase 3 study undertaken between Nov 10, 2010, and Nov 19, 2012, we enrolled women with recurrent epithelial ovarian cancer from 32 countries. Patient eligibility criteria included having been treated with three or fewer previous regimens, and a platinum-free interval of less than 12 months. We enrolled patients with a computerised interactive voice response system, and patients were randomly assigned using a permuted block method (block size of four) in a 1:1 ratio to receive weekly intravenous paclitaxel (80 mg/m(2)) plus either weekly masked intravenous placebo or trebananib (15 mg/kg). Patients were stratified on the basis of platinum-free interval (≥0 and ≤6 months vs >6 and ≤12 months), presence or absence of measurable disease, and region (North America, western Europe and Australia, or rest of world). The sponsor, investigators, site staff, and patients were masked to the treatment assignment. The primary endpoint was progression-free survival assessed in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT01204749, and is no longer accruing patients. FINDINGS: 919 patients were enrolled, of whom 461 were randomly assigned to the trebananib group and 458 to the placebo group. Median progression-free survival was significantly longer in the trebananib group than in the placebo group (7·2 months [5·8-7·4] vs 5·4 months [95% CI 4·3-5·5], respectively, hazard ratio 0·66, 95% CI 0·57-0·77, p<0·0001). Incidence of grade 3 or higher adverse events was similar between treatment groups (244 [54%] of 452 patients in the placebo group vs 258 [56%] of 461 patients in the trebananib group). Trebananib was associated with more adverse event-related treatment discontinuations than was placebo (77 [17%] patients vs 27 [6%], respectively) and higher incidences of oedema (294 [64%] patients had any-grade oedema in the trebananib group vs 127 [28%] patients in the placebo group). Grade 3 or higher adverse events included ascites (34 [8%] in the placebo group vs 52 [11%] in the trebananib group), neutropenia (40 [9%] vs 26 [6%]), and abdominal pain (21 [5%] vs 22 [5%]). We recorded serious adverse events in 125 (28%) patients in the placebo group and 159 (34%) patients in the trebananib group. There was a difference of 2% or less in class-specific adverse events associated with anti-VEGF therapy (hypertension, proteinuria, wound-healing complications, thrombotic events, gastrointestinal perforations), except bleeding, which was more common in the placebo group than in the trebananib group (75 [17%] vs 46 [10%]). INTERPRETATION: Inhibition of angiopoietins 1 and 2 with trebananib provided a clinically meaningful prolongation in progression-free survival. This non-VEGF anti-angiogenesis option for women with recurrent epithelial ovarian cancer should be investigated in other settings and in combination with additional agents. Although oedema was increased, typical anti-VEGF associated adverse events were not prominent. FUNDING: Amgen.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Recombinantes de Fusão/administração & dosagem , Idoso , Inibidores da Angiogênese/efeitos adversos , Angiopoietina-1/antagonistas & inibidores , Angiopoietina-2/antagonistas & inibidores , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Método Duplo-Cego , Edema/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Suspensão de Tratamento
9.
Gynecol Oncol ; 132(1): 23-7, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24219980

RESUMO

BACKGROUND: Most borderline ovarian tumors (BOTs) are cured with surgery. However BOTs with invasive implants have a poor prognosis with a mortality of 20-40%. The benefit of adjuvant chemotherapy (CT) in this setting remains poorly defined. METHODS: Retrospective study of serous BOT+invasive implants treated with adjuvant CT. RESULTS: 36 patients were referred with serous BOTs+invasive implants and treated with surgery and platinum-based CT between 06/1982 and 02/2011. 83% were stage III/IV. Tumors demonstrated microinvasion, micropapillary pattern or desmoplastic implants in 53%, 47% and 67% of cases, respectively. 8% had fertility-sparing surgery. Taking into account initial and completion surgeries, R0 was achieved in 84% (27/32) (NA, N=4). The majority (72%) received a combination of platinum+taxane. 11% of patients experienced a G3/G4 toxicity. 13 of 36 (36%) patients relapsed at a median of 27.3 months after diagnosis of invasive implants. Among 12 patients with histologically confirmed relapse, 8 patients progressed with invasive disease in the form of carcinoma or invasive implants. 5 year PFS/OS were 67%/96%. Neither microinvasion, micropapillary pattern, nor desmoplastic implants predicted relapse. In cases with evaluable disease, an objective response to chemotherapy was observed in 4 of 6 patients. CONCLUSION: This is the largest study of BOT with invasive implants treated with surgery and adjuvant platinum-based CT. Treatment was well tolerated and the invasive relapse rate was 22% (8/36). Although numbers are small, the objective responses suggest a possible role for adjuvant CT in BOTs with invasive implants.


Assuntos
Antineoplásicos/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Platina/uso terapêutico , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Resultado do Tratamento
10.
Int J Gynecol Cancer ; 24(9 Suppl 3): S5-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25341581

RESUMO

Since the early 1970s, the World Health Organization and the International Federation of Gynecology and Obstetrics have classified borderline ovarian tumors as an independent group of ovarian epithelial tumors. A consensus statement of the Gynecologic Cancer Intergroup is reported.


Assuntos
Oncologia , Neoplasias Ovarianas/patologia , Guias de Prática Clínica como Assunto , Terapia Combinada , Consenso , Feminino , Humanos , Neoplasias Ovarianas/classificação , Neoplasias Ovarianas/terapia , Sociedades Médicas
11.
Gynecol Oncol ; 130(1): 25-30, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23591401

RESUMO

OBJECTIVES: Sorafenib, an oral multikinase inhibitor of the VEGFR/PDGFR/Raf/MEK/ERK pathway, has shown potential activity in patients with recurrent ovarian cancer (OC). One strategy to prolong disease control and survival in patients with OC is maintenance therapy after achieving a complete response. A double-blind, randomized, placebo-controlled, phase II study to assess the efficacy and safety of maintenance therapy with sorafenib in the treatment of OC is presented. METHODS: Patients with epithelial OC or primary peritoneal cancer in complete remission were randomized to sorafenib 400mg BID or matching placebo. The primary endpoint was progression-free survival (PFS). RESULTS: Of 246 randomized patients, 93% had OC; baseline characteristics were balanced between treatment arms. There was no significant difference between sorafenib and placebo arms for PFS (median 12.7 vs 15.7 months; hazard ratio 1.09; 95% CI 0.72-1.63), although there was a notable imbalance in early censoring. The most common ≥ grade 3 adverse events (AEs) were hand-foot skin reaction (39.0% vs 0.8%) and rash (14.6% vs 0%). More patients receiving sorafenib versus placebo required dose reductions (67.5% vs 30.1%), resulting in a lower than planned median daily dose (median 584.6 vs 800.0mg). Treatment with sorafenib was of shorter duration (median 17.6 vs 51.9 weeks) with more frequent discontinuations due to AEs (37.4% vs 6.5%). CONCLUSIONS: Sorafenib 400mg BID cannot be recommended as maintenance therapy for patients with OC in complete remission. Assessment of efficacy was limited by the high rate of dose reductions and early discontinuations.


Assuntos
Niacinamida/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Idoso , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Terapia Combinada , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Neoplasias Ovarianas/cirurgia , Compostos de Fenilureia/efeitos adversos , Placebos , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Sorafenibe
12.
Curr Oncol Rep ; 15(6): 559-65, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24190831

RESUMO

Lymph node status is a major prognostic factor in endometrial cancer (EC). Sentinel lymph node (SLN) biopsy has been reported in EC for more than 15 years but has not yet been incorporated as a standard-of-care procedure in EC. Complex uterine drainage, the various modalities of tracer injection, and the lack of large prospective series may explain this situation. In this review, we report an SLN detection rate of 81.7 %, a 10.9 % rate of metastatic SLN involvement, and a false-negative rate of 12.3 % in the main clinical trials. Thirty-five percent of SLN metastases were low-volume disease (micrometastases or isolated tumor cells). These data raise the question of the clinical significance of low-volume disease in EC. SLN biopsy could allow upstaging in supposedly low- or intermediate-risk patients in whom adjuvant therapy could be omitted. Further studies are required to precise the interest on the survival of this procedure in this subset of patients.


Assuntos
Neoplasias do Endométrio/patologia , Biópsia de Linfonodo Sentinela , Feminino , Humanos , Metástase Linfática
13.
Oncologist ; 17(9): 1198-203, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22707515

RESUMO

INTRODUCTION: We describe the incidence, impact on survival, and the risk factors for symptomatic lymphoceles in patients with ovarian cancer. METHODS: This retrospective study includes patients with ovarian cancer who had complete cytoreductive surgery and para-aortic and pelvic lymphadenectomy performed in our institute from 2005 to 2011. Patients were classified into two groups: patients with symptomatic lymphoceles and a control group. RESULTS: During the study period, 194 patients with epithelial ovarian cancer underwent cytoreductive surgery and a lymphadenectomy without macroscopic residual disease. Fifty-four patients had symptomatic lymphoceles (28%). In the multivariate analysis, only supraradical surgery was significantly and independently associated with the risk of symptomatic lymphoceles occurring postoperatively. Median follow-up was 24.8 months (range, 1-74 months). Survival rates were not significantly different between the symptomatic lymphocele group and the control group. Two-year disease-free survival rates were 54% for the lymphocele group and 48% for the control group. Two-year overall survival rates were 90% for the lymphocele group and 88% for the control group. CONCLUSIONS: Symptomatic lymphoceles occur frequently after cytoreductive surgery in ovarian cancer. Supraradical surgery is an independent risk factor. The occurrence of symptomatic lymphoceles does not decrease survival. Nevertheless, further studies are needed to reduce the risk of lymphoceles in such patients.


Assuntos
Linfocele/epidemiologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Adulto , Idoso , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Excisão de Linfonodo/efeitos adversos , Linfocele/etiologia , Linfocele/patologia , Pessoa de Meia-Idade , Neoplasia Residual , Neoplasias Epiteliais e Glandulares/complicações , Neoplasias Epiteliais e Glandulares/cirurgia , Razão de Chances , Neoplasias Ovarianas/complicações , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
14.
Oncologist ; 16(2): 189-96, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21273510

RESUMO

BACKGROUND: To determine the prognosis of a micropapillary (MP) pattern in patients with stage II and stage III serous borderline tumor of the ovary (SBOT). METHODS: Review of patients with stage II and stage III SBOT treated or referred to our institution with characterization of an MP pattern and its clinical impact. RESULTS: In 1969-2006, 168 patients were reviewed. Fifty-six patients had SBOT-MP. The rate of conservative surgery was lower in the SBOT-MP group than in the typical SBOT group, but the rate of patients with more than three peritoneal sites with implants was higher in the SBOT-MP group. The rate of invasive implants was not statistically different between the two groups. Eighteen recurrences were observed (six of them in the form of invasive disease) in the SBOT-MP group. Only one death was observed. The overall survival times and recurrence-free intervals were similar in both groups. The only prognostic factor for recurrence in the SBOT-MP group was the use of conservative surgery. CONCLUSIONS: In the present series, an MP pattern doesn't appear to signify a poor prognosis. The only prognostic factor for recurrence in SBOT-MP was the use of conservative surgery. Further studies on the MP pattern are needed to evaluate prognosis and the results of conservative surgery.


Assuntos
Cistadenocarcinoma Papilar/patologia , Cistadenocarcinoma Papilar/cirurgia , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Adulto , Idoso , Cistadenocarcinoma Papilar/mortalidade , Cistadenocarcinoma Seroso/mortalidade , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Neoplasias Ovarianas/terapia , Ovário/patologia , Ovário/cirurgia , Lesões Pré-Cancerosas/patologia , Lesões Pré-Cancerosas/cirurgia , Prognóstico , Resultado do Tratamento , Adulto Jovem
15.
Ann Surg Oncol ; 18(1): 40-8, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20737216

RESUMO

BACKGROUND: To determine the prognosis and prognostic factors in a large series of mucinous borderline tumors of the ovary (MBOT). MATERIALS AND METHODS: A retrospective review of patients with MBOT treated or referred to our institution. Three inclusion criteria were defined: (1) centralized histological review by our expert pathologist, (2) exclusion of peritoneal pseudomyxoma and any synchronous malignant tumor in the abdominal cavity, and (3) available data on the management and outcomes of patients. RESULTS: From 1997 to 2004, 97 patients fulfilled inclusion criteria (95 stage I and 2 stage II disease). Of these, 9 patients had endocervical-like subtypes, 8 patients had stromal microinvasion, and 24 had intraepithelial carcinoma. Radical and conservative surgeries were performed, respectively, in 28 and 69 patients. After a median follow-up of 48 months, 13 patients had developed 14 recurrences: 7 were borderline and 7 were invasive lesions. The probability of recurrence in the form of carcinoma 5 and 10 years after the diagnosis was, respectively, 9 and 13%. The only prognostic factor for recurrence attaining statistical significance was the use of a cystectomy (compared with other surgeries relative risk [RR] = 5.6; P = 0.003; compared with salpingo-oophorectomy RR = 5.5; P = 0.012). CONCLUSIONS: In the present series of 97 MBOT, mainly early-stage disease and excluding peritoneal pseudomyxoma, the cumulative risk of recurrence in the form of invasive carcinoma at 10 years was 13%. MBOT do not appear to be such a "safe" disease. The only prognostic factor for recurrence was the use of a cystectomy, suggesting that a salpingo-oophorectomy should be preferred in cases of conservative treatment.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma in Situ/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Adenocarcinoma Mucinoso/cirurgia , Adolescente , Adulto , Idoso , Carcinoma in Situ/cirurgia , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos , Adulto Jovem
16.
Hum Reprod ; 26(4): 808-14, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21262776

RESUMO

BACKGROUND The aim of this study was to define determinants of fertility in patients treated conservatively for mucinous borderline ovarian tumours (MBOTs), and to compare outcomes after salpingo-oophorectomy or cystectomy. METHODS This was a retrospective cohort study of fertility results in a series of patients treated conservatively for MBOTs and desiring pregnancy. Conservative surgery was defined as preservation of the uterus and ovarian tissue in one or both adnexa(e). Fertility results were compared with patients who had undergone a cystectomy or a (salpingo-)oophorectomy. Only patients with a minimum of 1 year of follow-up were included. Epidemiological, surgical, histological parameters and other prognostic factors for fertility results were investigated. RESULTS A group of 31 patients who had been treated conservatively between 1997 and 2004 and who desired pregnancy were investigated. Patients were treated by unilateral salpingo-oophorectomy (USO) (n = 19) or cystectomy (n = 12). The 5-year recurrence-free survival rate was higher in the USO group compared with the cystectomy group (94.7 versus 49.1%, P = 0.041). Among the 31 women, 12 had become pregnant. The 5-year probabilities of pregnancy were comparable between the cystectomy and salpingo-oophorectomy groups (41.8 and 45.9%, respectively, P= 0.66). None of the other factors studied (epidemiological, surgical and histological parameters) were associated with fertility results. CONCLUSIONS The use of salpingo-oophorectomy rather than cystectomy should be preferred during conservative surgery for patients with MBOTs because it decreases the risk of recurrence and does not impair fertility.


Assuntos
Neoplasias Ovarianas/cirurgia , Adulto , Estudos de Coortes , Feminino , Fertilidade , Seguimentos , Humanos , Infertilidade Feminina/etiologia , Oncologia/métodos , Neoplasias Císticas, Mucinosas e Serosas/complicações , Neoplasias Císticas, Mucinosas e Serosas/cirurgia , Neoplasias Ovarianas/complicações , Ovariectomia/métodos , Gravidez , Estudos Retrospectivos , Resultado do Tratamento
17.
Am J Obstet Gynecol ; 204(5): 438.e1-7, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21349494

RESUMO

OBJECTIVE: This study was conducted to evaluate the prognosis value of lymph node involvement (LN positive) lymph node involvement for borderline ovarian tumor (BOT). STUDY DESIGN: This was a retrospective study on 49 patients treated at our institution for advanced-stage serous BOT (International Federation of Gynecology and Obstetrics [FIGO] III or IV). Pathological characteristics and survival were compared according to the lymph node status. The same analysis was performed on 1503 patients of the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: In our institution, 14 patients were LN positive. Eight patients have been upstaged after lymph node dissection. No patient has died during follow-up (median 53 months). LN positivity was not associated with recurrence. In the SEER registry, 93 patients (6.2%) had LN positivity. These patients were younger and with more advanced local extension. Survival curves were similar after adjustment for FIGO stage. CONCLUSION: Lymph node involvement does not appear as a prognosis factor for advanced-stage BOT.


Assuntos
Linfonodos/patologia , Metástase Linfática/patologia , Neoplasias Ovarianas/patologia , Adulto , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos Retrospectivos
18.
Oncologist ; 15(4): 405-15, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20332143

RESUMO

PURPOSE: The aim of this study was to evaluate the prognostic factors and morbidities of patients undergoing completion surgery for locally advanced-stage cervical cancer after initial chemoradiation therapy (CRT). PATIENTS AND METHODS: Patients fulfilling the following inclusion criteria were studied: stage IB2-IVA cervical carcinoma, tumor initially confined to the pelvic cavity on conventional imaging, pelvic external radiation therapy with delivery of 45 Gy to the pelvic cavity and concomitant chemotherapy (cisplatin, 40 mg/m(2) per week) followed by uterovaginal brachytherapy, and completion surgery after the end of radiation therapy including at least a hysterectomy. RESULTS: One-hundred fifty patients treated in 1998-2007 fulfilled the inclusion criteria. Prognostic factors for overall survival in the multivariate analysis were the presence and level of nodal spread (positive pelvic nodes alone: hazard ratio [HR], 2.03; positive para-aortic nodes: HR, 5.46; p < .001) and the presence and size of residual disease (RD) in the cervix (p = .02). Thirty-seven (25%) patients had 55 postoperative complications. The risk for complications was higher with a radical hysterectomy (p = .04) and the presence of cervical RD (p = .01). CONCLUSION: In this series, the presence and size of RD and histologic nodal involvement were the strongest prognostic factors. Such results suggest that the survival of patients treated using CRT for locally advanced cervical cancer could potentially be enhanced by improving the rate of complete response in the irradiated area (cervix or pelvic nodes) and by initially detecting patients with para-aortic spread so that treatment could be adapted in such patients. The morbidity of completion surgery is high in this context.


Assuntos
Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Quimioterapia Adjuvante , Intervalos de Confiança , Progressão da Doença , Feminino , França , Humanos , Histerectomia , Excisão de Linfonodo , Metástase Linfática , Pessoa de Meia-Idade , Morbidade , Análise Multivariada , Razão de Chances , Tomografia por Emissão de Pósitrons , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero/patologia , Adulto Jovem
19.
Gynecol Oncol ; 116(2): 157-62, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20109725

RESUMO

OBJECTIVE: This phase II investigated efficacy and tolerability of gefitinib in combination with paclitaxel (P) and carboplatin (C) for second-line treatment of patients (pts) with ovarian, tubal or peritoneal adenocarcinoma. PATIENTS AND METHODS: Women (>18 years) with platinum-resistant/refractory (relapsed<6 months), or platinum-sensitive (relapsed >6 months) disease after first-line platinum-based and P chemotherapy. Pts received 6-8 cycles of gefitinib (500 mg/day), P (175 mg/m(2) 3 h infusion) and C (AUC 5) every 3 weeks, followed by gefitinib alone. The primary endpoint was objective response rate (ORR) (RECIST or Rustin criteria). RESULTS: Sixty-eight patients (26 resistant/refractory and 42 sensitive) were enrolled (median age: 57 years). ORR and disease control rates were 19.2% and 69.2% for resistant/refractory, and 61.9% and 81.0%, for sensitive disease. Median time to progression and overall median survivals were 6.1 and 16.9 months for resistant/refractory and 9.2 and 25.7 months for sensitive disease. Grade 3/4 toxicities (in > or = 10% patients) were neutropenia (59%), diarrhea (25%), leukopenia (22%), anemia (13%), and acne (13%). Two secondary myelodysplastic syndromes (MDS) and one secondary acute leukemia occurred during treatment, and one MDS 34 months after treatment discontinuation. CONCLUSION: Gefitinib, administered in combination with paclitaxel and carboplatin, provides a good clinical response but associated with an increased risk of hematologic disorders.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias das Tubas Uterinas/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Intervalo Livre de Doença , Feminino , Gefitinibe , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos
20.
Int J Gynecol Cancer ; 20(6): 965-70, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20683403

RESUMO

BACKGROUND: Surgical management of primary or recurrent ovarian cancer with extensive upper abdominal disease may require splenectomy to achieve complete cytoreduction. The aims of this series were to correlate the macroscopic exploration with the microscopic analysis of the spleen and to evaluate the morbidity of patients submitted to this procedure for primary and recurrent disease. METHODS: Data concerning patients who underwent splenectomy at the time of management of the primary (initial group) or recurrent disease were reviewed. The characteristics and survival of patients were analyzed. The correlation between macroscopic suspected lesion and histological results and morbidity according to the Dindo classification was studied. RESULTS: From 1995 to 2008, 58 patients (42 in the initial group and 16 in the recurrence group) underwent a splenectomy in our institution. Except for 3 cases requiring splenectomy for hemostatic reasons, the macroscopically suspected splenic lesion was confirmed by histology in 32 (80%) of 40 cases in the initial group and in 14 (93%) of 15 cases in the recurrence group. Eighteen patients (26.5%) had a morbidity grade strictly superior to 2, and in all the factors we tested, only pelvic posterior exenteration was a risk factor for high morbidity (P = 0.02). CONCLUSIONS: When splenic lesions are macroscopically suspected during cytoreductive surgery for an ovarian cancer, most of the time the disease is confirmed by histology. When required to accomplish complete cytoreduction, splenectomy seemed to be justified.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Esplenectomia , Neoplasias Esplênicas/patologia , Adulto , Fatores Etários , Idoso , Biópsia por Agulha , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Ovariectomia , Estudos Retrospectivos , Medição de Risco , Neoplasias Esplênicas/secundário , Análise de Sobrevida , Carga Tumoral
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