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1.
Gynecol Oncol ; 190: 264-271, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39265464

RESUMO

OBJECTIVE: Adjuvant radiotherapy to the vulva in vulvar squamous cell carcinoma (VSCC) is frequently performed albeit strong evidence is lacking. This systematic review aims to summarize the current literature on this topic. METHODS: 19 retrospective studies were included and analyzed, focusing on the primary outcome of local recurrence. RESULTS: The publications present conflicting results. While the benefit of adjuvant radiotherapy to the groins in case of node-positive VSCC is well established, the indication criteria and effectiveness of adjuvant radiotherapy to the vulva remain unclear. Based on the studies included in this review, the current evidence suggests that adjuvant radiotherapy to the vulva might not significantly reduce the risk of recurrence or only in certain subgroups. CONCLUSION: Most of the studies do not consider individual risk factors such as HPV status, resection margin, lymph node stage, grading and others. As a result, the comparability and reliability of these findings are limited. This review aims to highlight the need of further research addressing the risk stratification, considering both oncologic risk factors and adverse events.

2.
Arch Gynecol Obstet ; 309(4): 1561-1567, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38081959

RESUMO

PURPOSE: Persistent high-risk HPV infection is associated with an elevated risk for prevalent CIN II + despite normal cytology (NILM). Our study aims to evaluate the clinical relevance of a persistent high-risk HPV infection without cytologic changes in women aged ≥ 65 and to determine the role of colposcopy for triage in these cases. METHODS: 211 patients aged ≥ 65 with persistent HPV infection and normal cytology (NILM) who presented for colposcopy at five certified centers between January 2021 and April 2022 were included in the study. Colposcopic findings, HPV subtypes, when available, histology and p16/Ki67 staining were assessed as well as individual risk factors such as smoking and previous HPV-related surgery. RESULTS: 87.7% (185/211) of the included women had a type 3 transformation zone. In 83.4% (176/211), a biopsy was taken [thereof 163 endocervical curettages (ECC)]. In 35/211 women (16.6%), sampling was not possible during colposcopy due to an inaccessible cervix, pain during examination or obliteration of the cervical canal. Out of these, 6 women received a diagnostic excision. CIN II + was detected in 10.6% of all histologies (excisional or biopsy) (20/182). 50% of the women with a CIN II + where HPV 16 positive. Taking only the women diagnosed with CIN III or AIS into account, (n = 12) 75% were HPV 16 positive. Interestingly, 80% of the women with CIN II + had an abnormal cytology when repeatedly taken during colposcopy, vice versa an endocervical lesion was diagnosed in 53% of women with abnormal repeat cytology (27/51). CONCLUSION: The prevalence of CIN II + in women is ≥ 65 with persistent hr HPV infection but NILM cytology is similar to that in younger women. However, more than 85% of the women have a type 3 transformation zone. Colposcopy is, therefore, not helpful to diagnose the women who need treatment in this age group.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Humanos , Feminino , Colposcopia , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/complicações , Triagem , Displasia do Colo do Útero/patologia , Papillomaviridae
3.
Arch Gynecol Obstet ; 305(1): 233-240, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34387725

RESUMO

BACKGROUND: The value of pelvic lymphadenectomy (LAE) has been subject of discussions since the 1980s. This is mainly due to the fact that the relation between lymph node involvement of the groin and pelvis is poorly understood and therewith the need for pelvic treatment in general. PATIENTS AND METHODS: N = 514 patients with primary vulvar squamous cell cancer (VSCC) FIGO stage ≥ IB were treated at the University Medical Center Hamburg-Eppendorf between 1996 and 2018. In this analysis, patients with pelvic LAE (n = 21) were analyzed with regard to prognosis and the relation of groin and pelvic lymph node involvement. RESULTS: The majority had T1b/T2 tumors (n = 15, 78.9%) with a median diameter of 40 mm (11-110 mm). 17/21 patients showed positive inguinal nodes. Pelvic nodal involvement without groin metastases was not observed. 6/17 node-positive patients with positive groin nodes also had pelvic nodal metastases (35.3%; median number of affected pelvic nodes 2.5 (1-8)). These 6 patients were highly node positive with median 4.5 (2-9) affected groin nodes. With regard to the metastatic spread between groins and pelvis, no contralateral spread was observed. Five recurrences were observed after a median follow-up of 33.5 months. No pelvic recurrences were observed in the pelvic nodal positive group. Patients with pelvic metastasis at first diagnosis had a median progression-free survival of only 9.9 months and overall-survival of 31.1 months. CONCLUSION: A relevant risk for pelvic nodal involvement only seems to be present in highly node-positive disease, therefore pelvic staging (and radiotherapy) is probably unnecessary in the majority of patients with node-positive VSCC.


Assuntos
Neoplasias Vulvares , Feminino , Virilha/patologia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Vulvares/patologia
4.
Oncogenesis ; 6(5): e331, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28504691

RESUMO

Intraabdominal tumor dissemination is a major hallmark of epithelial ovarian cancer (EOC), but the underlying mechanisms have not been fully elucidated. The CXCR3 chemokine receptor supports migration of tumor cells to metastatic sites, but its role in ovarian cancer metastasis is largely unknown. Herein, we first screened two independent cohorts of high-grade serous ovarian cancers (HGSCs, discovery set n=60, validation set n=117) and 102 metastatic lesions for CXCR3 expression. In primary tumors, CXCR3 was particularly overexpressed by tumor cells at the invasive front. In intraabdominal metastases, tumor cells revealed a strong CXCR3 expression regardless of its expression in the corresponding primary tumor, suggesting a selection of CXCR3-overexpressing cancer cells into peritoneal niches. In support of this, CXCR3 mediated the migration of tumor cell lines OVCAR3 and SKOV3 toward malignant ascites, which was inhibited by a monoclonal anti-CXCR3 antibody in vitro. These results were prospectively validated in ascites-derived tumor cells from EOC patients ex vivo (n=9). Moreover, tumor cell-associated overexpression of CXCR3 in advanced ovarian cancer patients was associated with a reduced progression-free survival (PFS) and overall survival (OS), which remained independent of optimal debulking, age, FIGO stage and lymph node involvement (PFS: hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.30-3.45, P=0.003; OS: HR 2.36, 95% CI 1.50-3.71, P<0.001). These results in ovarian cancer patients identify CXCR3 as a potential new target to confine peritoneal spread in ovarian cancer after primary cytoreductive surgery.

5.
Arch Gynecol Obstet ; 295(5): 1259-1268, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28357559

RESUMO

INTRODUCTION: The purpose of this study was to systematically analyze the effect of transvaginal ultrasonography in an asymptomatic female population as an annual screening procedure with regard to mortality data. Studies were evaluated descriptively on their strengths and weaknesses considering the methods and results. METHODS: We evaluated 632 international studies by selecting only randomized controlled trials (RCTs). Three RCTs concerning transvaginal ultrasonography were found, performed in Japan, the USA, and Great Britain. DISCUSSION: Currently, no clear recommendation for the screening for ovarian cancer in an asymptomatic population can be given based on these three studies. The authors could not show a change in mortality using transvaginal ultrasonography for annual screening. CONCLUSION: An annual palpation does not offer a beneficial effect. The development of new ultrasound machines with higher image resolution in combination with a well-standardized algorithm for ovarian cancer in upcoming years might provide an improvement regarding mortality. The current studies do not show a benefit in screening an asymptomatic population annually with transvaginal ultrasonography, but the most recent publication showed a trend toward lower mortality in patients who underwent screening after 7-14 years of follow-up. Nevertheless, all three heterogeneous RCTs had weaknesses in their methods and therefore they neither contradict the general recommendation for screening in an asymptomatic population nor do they support it.


Assuntos
Detecção Precoce de Câncer/métodos , Neoplasias Ovarianas/diagnóstico por imagem , Feminino , Humanos , Ultrassonografia , Vagina
7.
Br J Cancer ; 112(4): 660-6, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25562434

RESUMO

BACKGROUND: Incomplete surgical staging is a negative prognostic factor for patients with borderline ovarian tumours (BOT). However, little is known about the prognostic impact of each individual staging procedure. METHODS: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 at 24 German AGO centres were analysed. In 559 patients with serous BOT and adequate ovarian surgery, further recommended staging procedures (omentectomy, peritoneal biopsies, cytology) were evaluated applying Cox regression models with respect to progression-free survival (PFS). RESULTS: For patients with one missing staging procedure, the hazard ratio (HR) for recurrence was 1.25 (95%-CI 0.66-2.39; P=0.497). This risk increased with each additional procedure skipped reaching statistical significance in case of two (HR 1.95; 95%-CI 1.06-3.58; P=0.031) and three missing steps (HR 2.37; 95%-CI 1.22-4.64; P=0.011). The most crucial procedure was omentectomy which retained a statistically significant impact on PFS in multiple analysis (HR 1.91; 95%-CI 1.15-3.19; P=0.013) adjusting for previously established prognostic factors as FIGO stage, tumour residuals, and fertility preservation. CONCLUSION: Individual surgical staging procedures contribute to the prognosis for patients with serous BOT. In this analysis, recurrence risk increased with each skipped surgical step. This should be considered when re-staging procedures following incomplete primary surgery are discussed.


Assuntos
Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/patologia , Procedimentos Cirúrgicos em Ginecologia , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenoma Seroso/epidemiologia , Cistadenoma Seroso/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Adulto Jovem
8.
Ann Oncol ; 25(7): 1320-1327, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24618151

RESUMO

BACKGROUND: Approximately one-third of all borderline ovarian tumours (BOT) are diagnosed in patients with child-bearing potential. Detailed information regarding their specific characteristics and prognostic factors is limited. METHODS: Clinical parameters of BOT patients treated between 1998 and 2008 in 24 German centres were retrospectively investigated. Central pathology review and prospective follow-up were carried out. Patients <40 versus ≥40 years were analysed separately and then compared regarding clinico-pathological variables and prognosis. RESULTS: A total of 950 BOT patients with a median age of 49.1 (14.1-91.5) years were analysed [280 patients <40 years (29.5%), 670 patients ≥40 years (70.5%)]. Fertility-preserving surgery was carried out in 53.2% (149 of 280) of patients <40 years with preservation of the primarily affected ovary in 32 of these 149 cases (21.5%). Recurrence was significantly more frequent in patients <40 years (19.0% versus 10.1% 5-year recurrence rate, P < 0.001), usually in ovarian tissue, whereas disease-specific overall survival did not differ between the subgroups. In case of recurrent disease, malignant transformation was less frequent in younger than in older patients (12.0% versus 66.7%, P < 0.001), mostly presenting as invasive peritoneal carcinomatosis. Multivariate analysis for patients <40 years identified advanced International Federation of Gynecology and Obstetrics (FIGO) stage and fertility-sparing approach as independent prognostic factors negatively affecting progression-free survival (PFS) while, for patients ≥40 years, higher FIGO stage and incomplete staging was associated with impaired PFS. CONCLUSIONS: Despite favourable survival, young BOT patients with child-bearing potential are at higher risk for disease recurrence. However, relapses usually remain BOT in the preserved ovaries as opposed to older patients being at higher risk for malignant transformation in peritoneal or distant localisation. Therefore, fertility-sparing approach can be justified for younger patients after thorough consultation.


Assuntos
Fatores Etários , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Ann Oncol ; 23(8): 1979-1985, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22734013

RESUMO

BACKGROUND: Malignant ascites (MA) is associated with poor prognosis and limited palliative therapeutic options. Therefore, quality of life (QoL) assessment is of particular importance to demonstrate new treatment value. Following the demonstration of the superiority of catumaxomab and paracentesis over paracentesis on puncture-free survival, this analysis aimed at comparing deterioration in QoL between both the treatment options. PATIENTS AND METHODS: In a randomised, multicentre, phase II/III study of patients with MA due to epithelial cell adhesion molecule (EpCAM) positive cancer, the QoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items (EORTC QLQ-C30) questionnaire at screening, 1, 3 and 7 months after treatment and in the case of re-puncture on the day of paracentesis. Time to first deterioration in QoL was defined as a decrease in the QoL score of at least five points and compared between the catumaxomab (n=160) and control (n=85) groups using the log-rank test and Cox proportional hazards models adjusted for baseline score, country and primary tumour type. RESULTS: Deterioration in QoL scores appeared more rapidly in the control than in the catumaxomab group (median 19-26 days versus 47-49 days). The difference in time to deterioration in QoL between the groups was statistically significant for all scores (P<0.01). The hazard ratios ranged from 0.08 to 0.24 (P<0.01). CONCLUSIONS: Treatment with catumaxomab delayed deterioration in QoL in patients with MA. Compared with paracentesis alone, catumaxomab enabled patients to benefit from better QoL for a prolonged survival period.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Ascite/patologia , Ascite/terapia , Neoplasias/patologia , Neoplasias/terapia , Paracentese/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Ascite/metabolismo , Moléculas de Adesão Celular/metabolismo , Terapia Combinada , Molécula de Adesão da Célula Epitelial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Modelos de Riscos Proporcionais , Qualidade de Vida , Adulto Jovem
10.
Gynecol Oncol ; 123(1): 27-32, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21733566

RESUMO

OBJECTIVE: The aim of this study was to select the best catumaxomab regimen for further investigation in ovarian cancer based on confirmed tumour response. METHODS: Randomised open-label phase IIa study in women with platinum-resistant or -refractory epithelial ovarian cancer. Catumaxomab (6-hour intraperitoneal infusion on days 0, 3, 7 and 10) was administered at a low (10, 10, 10 and 10 µg) or high dose (10, 20, 50 and 100 µg). Responders were patients with either a complete (CR) or partial (PR) response. RESULTS: Forty-five patients were randomised to receive either low dose (23) or high dose (22). There were no responders in the low-dose versus one patient (5%) in the high-dose group with a PR. In the low-dose group, two patients (9%) had stable disease compared with five patients (23%) in the high-dose group. Catumaxomab was well tolerated and there was no difference between the dose groups in the incidence of treatment-induced adverse events, the most common of which were gastrointestinal and injection-site reactions. CONCLUSION: Catumaxomab had modest activity in platinum-resistant ovarian cancer. The high-dose regimen was associated with a slightly better therapeutic index than the low dose regimen.


Assuntos
Anticorpos Biespecíficos/administração & dosagem , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Epitelial do Ovário , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Infusões Parenterais , Pessoa de Meia-Idade , Compostos Organoplatínicos/farmacologia
11.
Ann Oncol ; 22(4): 877-883, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20924077

RESUMO

BACKGROUND: Primary tumor levels of serine proteases of the kallikrein-related peptidases (KLK) family as well as urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 impact disease course in ovarian cancer. The changes in levels of these factors from primary tumor to omentum metastasis ('level differentials') could thus be associated with metastastic processes. PATIENTS AND METHODS: Protein levels of seven tissue KLK (KLK5-8, 10, 11, 13), uPA, and PAI-1 were determined in extracts of primary tumor tissue and corresponding omentum metastasis of 54 ovarian cancer patients. RESULTS: Higher level differentials of KLK5-8, 10-11, and uPA were associated with residual tumor >10 mm. Residual tumor and larger level differentials of KLK5-7, 10, and uPA were associated with disease progression in the whole cohort. Remarkably, level differentials of KLK5-8 and 10-11 strongly impacted disease progression even in patients with residual tumor mass ≤10 mm; hence, the observed impact of level differentials in KLK5-7 and 10 on disease progression was not simply attributable to their association with surgical success. CONCLUSION: Since they impact both surgical outcome and survival in advanced ovarian cancer, measurement of level differentials could support clinical decisions on surgical and systemic therapy or help in patient selection for novel targeted therapies.


Assuntos
Omento/patologia , Neoplasias Ovarianas/metabolismo , Peptídeo Hidrolases/biossíntese , Neoplasias Peritoneais/metabolismo , Inibidor 1 de Ativador de Plasminogênio/biossíntese , Ativador de Plasminogênio Tipo Uroquinase/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Progressão da Doença , Feminino , Humanos , Calicreínas/biossíntese , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Prognóstico , Estudos Retrospectivos
12.
Urologe A ; 49(9): 1142, 1144-8, 2010 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-20706705

RESUMO

Male breast cancer (male BC) accounts for <1% of all cancers in men, showing an increasing incidence with a peak in the sixth decade. Overall, men experience a worse prognosis than women, probably due to an advanced stage together with the higher age at diagnosis of male patients. Major risk factors for developing male BC include clinical disorders involving hormonal imbalances (excess of estrogen or a deficiency of testosterone as seen in patients with Klinefelter syndrome) and a positive family history for breast cancer. About 90% of male BC are invasive ductal carcinomas. Standard treatment for localized cancer is surgical removal. Adjuvant radiation and systemic therapy are the same as in women with breast cancer. Male BC expresses hormone receptors in about 90% of cases; therefore, tamoxifen is a therapeutic option. A future challenge for the urologist or andrologist is to diagnose the disease at an early stage to improve prognosis.


Assuntos
Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/terapia , Técnicas de Diagnóstico Urológico , Tamoxifeno/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama Masculina/mortalidade , Humanos , Masculino , Prevalência
13.
Ann Surg Oncol ; 16(5): 1324-30, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19225844

RESUMO

BACKGROUND: Almost all retrospective trials pointed out that a benefit of surgery for recurrent ovarian cancer may be limited to patients in whom a macroscopic complete resection could be achieved. Peritoneal carcinomatosis has been reported to be either a negative predictor for resectability or a negative prognostic factor, or both. The role of peritoneal carcinomatosis in a multicenter trial was investigated. METHODS: Exploratory analysis of the DESKTOP I trial (multicenter trial of patients undergoing surgery for recurrent ovarian cancer, 2000 to 2003). RESULTS: A total of 125 patients (50%) who underwent surgery for recurrent ovarian cancer had peritoneal carcinomatosis. Univariate analyses showed worse overall survival for patients with peritoneal carcinomatosis compared with patients without carcinomatosis (P < .0001). Patients with and without peritoneal carcinomatosis had a complete resection rate of 26% and 74%, respectively (P < .0001). This corresponded with the observation that patients with complete resection had a better prognosis than those with minimal residual disease of 1 to 5 mm, which commonly reflects peritoneal carcinomatosis (P = .0002). However, patients who underwent complete resection, despite peritoneal carcinomatosis, had a 2-year survival rate of 77%, which was similar to the 2-year survival rate of patients with completely debulked disease who did not have peritoneal carcinomatosis (81%) (P = .96). Analysis of prognostic factors did not show any independent effect of peritoneal carcinomatosis on survival in patients who underwent complete resection. CONCLUSIONS: Peritoneal carcinomatosis was a negative predictor for complete resection but had no effect on prognosis if complete resection could be achieved. Improving surgical skills might be one step to increase the proportion of patients who might benefit from surgery for recurrent disease.


Assuntos
Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Bases de Dados como Assunto , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/secundário , Prognóstico , Fatores de Risco
14.
Cancer Chemother Pharmacol ; 64(3): 585-91, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19156414

RESUMO

PURPOSE: Pegylated liposomal doxorubicin (PLD, CAELYX) has demonstrated activity in several phase-III trials and has been approved for the therapy of relapsed ovarian cancer after platinum treatment. Aim of this observational study was to analyze the efficacy and toxicity profile of PLD under routine clinical conditions and without the general restrictions of defined inclusion and exclusion criteria of clinical trials. METHODS: Between 2003 and 2005, a total of 190 patients with relapsed ovarian cancer were enrolled. 183 patients were available for evaluation; dose-intensity, modifications, treatment duration, toxicities and response were systematically analyzed. RESULTS: The median patient age was 62 years (range 23-86 years). 45.4% of the patients received PLD as second-line therapy and a median of four courses per patient were administered. The median dose of PLD was 40 mg/m(2), most frequently used every 4 weeks (68.8%). Grade 3 Leucopenia (1.6%) and grade 3 and 4 thrombocytopenia (0.5%) were the most frequent hematological toxicities. The most frequent non-hematological toxicities were skin toxicity, pain and nausea, which were observed in 38.8, 41 and 45.9% of the patients, respectively. Twenty-seven percent of the patients showed a response to therapy with 6.9% achieving complete remission and 20.1% achieving partial remission. 37.7% achieved a stable disease. The median duration of response for all patients was 4.8 months (range 0-51.8 months). Median progression-free interval and overall survival were 5.8 months (95% CI 5.1-6.6 months) and 16.6 months (95% CI 13.9-22.6 months), respectively. CONCLUSIONS: PLD is safe and effective in patients with relapsed ovarian cancer, even after numerous previous treatment regimens. A dose of 40 mg/m(2) every 28 days seems to be an effective and well-tolerated therapeutic option in advanced ovarian cancer with a low incidence of hematological toxicities and acceptable non-hematological toxicities.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Doxorrubicina/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Alemanha/epidemiologia , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Indução de Remissão/métodos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
15.
Br J Cancer ; 98(2): 489-95, 2008 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-18026186

RESUMO

Epithelial ovarian cancer is the leading cause of death among female genital malignancies. Reduced expression of the cell adhesion molecule E-cadherin was previously shown to be associated with adverse prognostic features. The role of the E-cadherin repressor Snail in ovarian cancer progression remains to be elucidated. We analysed formalin-fixed and paraffin-embedded specimens of 48 primary ovarian tumours and corresponding metastases for expression of E-cadherin and Snail by immunohistochemistry. We found a significant correlation between E-cadherin expression in primary cancers and their corresponding metastases (P<0.001). This correlation was found for Snail expression as well (P<0.001). There was a significant (P=0.008) association of reduced E-cadherin expression in primary ovarian cancer with shorter overall survival. Similarly, Snail expression in corresponding metastases (P=0.047) was associated with reduced overall survival of the patients. Additionally, the group of patients showing reduced E-cadherin and increased Snail immunoreactivity in primary tumours and corresponding metastases, respectively, had a significantly higher risk of death (P=0.002 and 0.022, respectively) when compared to the patient group with the reference expression profile E-cadherin positive and Snail negative. Taken together, the results of our study show that the E-cadherin repressor Snail is associated with lower overall survival of ovarian cancer patients.


Assuntos
Carcinoma/genética , Carcinoma/mortalidade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Fatores de Transcrição/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Caderinas/genética , Carcinoma/patologia , Progressão da Doença , Regulação para Baixo , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Análise por Pareamento , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Ovarianas/patologia , Proteínas Repressoras/genética , Fatores de Transcrição da Família Snail , Análise de Sobrevida
16.
Gynecol Oncol ; 107(3): 541-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17884152

RESUMO

OBJECTIVE: To evaluate long-term outcome, risk factors, and causes of death in stage I-IIIA endometrial carcinoma (EC) patients treated only with adjuvant vaginal brachytherapy (VB) and to clarify for which subgroups of patients it is safe to omit external-beam radiotherapy (EBRT). METHODS: Out of 224 EC patients receiving postoperative radiotherapy between 1990 and 2002, 138 had VB alone in curative intent (FIGO [2002]: 85%I, 12%II, 3%IIIA; 18 low risk [IA G1-2, IB G1], 103 intermediate risk [IB G2-3, IC G1-2, IIA-B G1-2], 17 high risk [IC G3, IIIA]). After surgery+/-lymphadenectomy, HDR-brachytherapy prescription (in 95.7% of patients) was 3x10 Gy to the surface or 3x5 Gy at 5 mm tissue depths. RESULTS: Median follow-up was 107 months (range 3-185). Three intermediate and 7 high risk-patients relapsed. The 10-year vaginal control was 99.2%, locoregional control was 95.2% (low/intermediate/high risk: 100%/98.9%/68.8%), and disease-free survival (DFS) was 91.7% (100%/96.8%/55.2%). Risk factors for poor DFS were lymphovascular space invasion, > or = 50% myometrial invasion (univariate, p<0.05), pathological FIGO-stage, and grade 3 (uni-/multivariate, p<0.05). Leading causes of deaths (n=41) were cardiovascular disease (29%) and other malignancies (24%) ahead of EC (19.5%). The 10-year overall survival was 68.5% and the disease-specific survival was 92.4%. Thirty-five secondary tumors in 31 patients led to a higher actuarial death rate (10-year 9.9%, 15-year 17.7%) than EC (7.6%). CONCLUSIONS: Restricting adjuvant therapy to VB alone seems to be safe in low and intermediate risk EC and can be recommended. As death rarely relates to early-stage EC, value of adjuvant therapy is probably better reflected by DFS rather than by overall survival.


Assuntos
Braquiterapia/métodos , Neoplasias do Endométrio/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Vagina
17.
Int J Gynecol Cancer ; 16(5): 1756-60, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17009967

RESUMO

The German Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) and the two German cooperative study groups (AGO-OVAR and NOGGO) performed a review of the currently available literature on intraperitoneal first-line treatment in advanced ovarian cancer to consider if this new option should be incorporated into the German guidelines for treatment of ovarian cancer.


Assuntos
Antineoplásicos/administração & dosagem , Infusões Parenterais/métodos , Neoplasias Ovarianas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Ensaios Clínicos como Assunto , Feminino , Alemanha , Humanos , Guias de Prática Clínica como Assunto
18.
Zentralbl Gynakol ; 128(4): 202-6, 2006 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-16835814

RESUMO

Recently, the publication of the GOG 172 trial led to intraperitoneal (i. p.) chemotherapy in patients with ovarian cancer being regarded as potential new standard. The AGO Kommission Ovar, AGO-OVAR and NOGGO disagree with this view. In the GOG 172 study, several variables were mixed, and i. p.-therapy was not compared to the current standard paclitaxel plus carboplatin. The analysis was not based on an intention-to-treat (ITT) population, while even the slightest changes of significant results could lead to the elimination of their significance. Furthermore, the GOG 172 trial did not provide any details on second-line treatment which could have an impact on overall survival. High toxicity and the low number of cycles in i. p.-therapy might call the significant effect into question. The low median time of survival of the GOG 172 trial in the control arm (49.7 months) diverges from comparable collectives of three AGO-OVAR trials and the GOG 158 study (56.5-59.5 months). If the result of the GOG 172 trial had been similar, there would not have been any significance in comparison to i. p.-therapy. In order to change the current standard, it would be necessary to base the analysis on an ITT-population, provide details about second-line therapy, rule out bias regarding second-line therapy and to develop less toxic regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Ensaios Clínicos Controlados como Assunto , Feminino , Humanos , Injeções Intraperitoneais , Estudos Multicêntricos como Assunto , Neoplasias Ovarianas/mortalidade , Cooperação do Paciente , Análise de Sobrevida
19.
Ann Oncol ; 17(6): 957-61, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16600975

RESUMO

BACKGROUND: The obvious benefit of pegylated liposomal doxorubicin (PLD) for tumour control in recurrent ovarian cancer is frequently offset by severe palmar-plantar erythrodysesthesia (PPE). There is evidence that dose reduction from 50 to 40 mg/m(2) reduces the incidence of PPE without compromising cytotoxic activity. We set out to investigate whether biweekly application further improves the therapeutic index of PLD. PATIENTS AND METHODS: Patients with recurrent ovarian cancer after surgery and adjuvant chemotherapy with platinum and taxane compounds were eligible to participate in this multi-institutional phase II study. PLD was administered at a dose of 20 mg/m(2) every two weeks. Eligible patients had ECOG performance status of < or =2, and sufficient organ function. We employed an optimized two-stage design to test the hypothesis that biweekly application of PLD reduces the frequency of grade III and IV PPE from 25% to 10%. Response and survival were addressed descriptively. RESULTS: Between October 2001 and February 2004, 64 patients with median age of 59 (range 38-81) years were recruited onto this trial. We evaluated 553 (median 7, range 1-25) courses of PLD treatment. Most patients were in their third or fourth line of chemotherapy. PPE was noted in 30 patients (47.6%), but only three participants progressed to grade 3 severity (4.7%, 95% confidence interval 1.0-13.1%). Partial response, stable disease, and tumour progression were observed in 5, 13, and 24 patients, respectively. Median overall and progression-free survival were 18.2 (range, 1.4-34.0) and 4.3 (range 0.5-22.3) months. CONCLUSIONS: Biweekly PLD may reduce the incidence of PPE while retaining efficacy in relapsed ovarian cancer. Our data support the need for a randomized trial to strengthen these assumptions.


Assuntos
Doxorrubicina/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Doxorrubicina/toxicidade , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Seleção de Pacientes , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/toxicidade , Recidiva
20.
Zentralbl Gynakol ; 128(1): 11-7, 2006 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-16450281

RESUMO

Recommendations for diagnosis and treatment of malignant ovarian tumors with regard to the most recent data were worked out in a consensus process and valued by level of evidence (LoE) and grade of recommendation (GoR) of the Canadian Task Force for Preventive Health Care by the members of the Kommission Ovar der Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) in June 2005. A short version of these guidelines is presented.


Assuntos
Neoplasias Ovarianas/diagnóstico , Idoso , Terapia Combinada , Medicina Baseada em Evidências , Feminino , Alemanha , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Taxa de Sobrevida
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