RESUMEN
BACKGROUND: Pelvic exenteration may be the only curative treatment for some patients with primary advanced or recurrent vulvar cancer but is associated with high morbidity. This study evaluated the clinical outcome of patients treated at a centralized service in Norway. METHODOLOGY: This retrospective study included patients treated with pelvic exenteration for primary locally advanced or recurrent vulvar cancer between 1996 and 2019 at Oslo University Hospital, Norway. Complications were coded according to the contracted Accordion classification. Relapse free survival (RFS), cancer specific survival (CSS) and overall survival (OS) were estimated with the Kaplan Meier method. RESULTS: The 30 patients were followed for a median of 4.94 years (95%CI: 3.37-NR). Exenteration due to primary vulvar cancer was carried out in 16 (53%) patients, 14 (47%) had recurrent vulvar cancer. Free histopathological margins were achieved in 28 (93%) patients. The 90 days morbidity for grade 3 complications was 63%, predominantly wound/surgical flap infections, 7% had no complications. 90 days mortality was 3%. Five-year RFS was 26% (95% CI 8-48%), OS was 50% (95%CI: 29-69%) and CSS was 64% (95% CI 43-79%). There was no significant difference in survival between patients with primary vs recurrent disease. The 3-year CSS for patients with negative lymph nodes and positive lymph nodes was 70% (95% CI 47-84%) and 30% (95% CI 1-72%), respectively. CONCLUSIONS: Acceptable oncologic outcomes after pelvic exenteration for primary and recurrent vulvar cancer can be achieved if surgery is centralized. Careful patient selection is imperative due to significant postoperative morbidity and considerable risk of relapse.
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Exenteración Pélvica , Neoplasias de la Vulva , Femenino , Humanos , Neoplasias de la Vulva/cirugía , Neoplasias de la Vulva/patología , Estudios Retrospectivos , Exenteración Pélvica/métodos , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/cirugía , Morbilidad , Complicaciones Posoperatorias/etiología , Resultado del TratamientoRESUMEN
PURPOSE OF THE REVIEW: More than 50% of all gynaecological cancers can be classified as rare tumours (defined as an annual incidence of <6 per 100,000) and such tumours represent an important challenge for clinicians. RECENT FINDINGS: Rare cancers account for more than one fifth of all new cancer diagnoses, more than any of the single common cancers alone. Reviewing the RARECAREnet database, some of the tumours occur infrequently, whilst others because of their natural history have a high prevalence, and therefore appear to be more common, although their incidence is also rare. Harmonization of medical practice, guidelines and novel trials are needed to identify rare tumours and facilitate the development of new treatments. Ovarian tumours are the focus of this review, but we comment on other rare gynaecological tumours, as the diagnosis and treatment challenges faced are similar. FUTURE: This requires European collaboration, international partnerships, harmonization of treatment and collaboration to overcome the regulatory barriers to conduct international trials. Whilst randomized trials can be done in many tumour types, there are some for which conducting even single arm studies may be challenging. For these tumours alternative study designs, robust collection of data through national registries and audits could lead to improvements in the treatment of rare tumours. In addition, concentring the care of patients with rare tumours into a limited number of centres will help to build expertise, facilitate trials and improve outcomes.
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Atención a la Salud/organización & administración , Cooperación Internacional , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/terapia , Calidad de la Atención de Salud , Enfermedades Raras/epidemiología , Enfermedades Raras/terapia , Ensayos Clínicos como Asunto , Europa (Continente) , Femenino , Humanos , Incidencia , Prevalencia , Tasa de SupervivenciaRESUMEN
BACKGROUND: Data on CA-125 as a predictor of disease progression (PD) in ovarian cancer come predominantly from patients with platinum-sensitive disease receiving chemotherapy alone. We assessed concordance between CA-125-defined and RECIST-defined PD using data from the Gynecologic Cancer InterGroup (GCIG) randomized phase III AURELIA trial in platinum-resistant ovarian cancer (PROC). PATIENTS AND METHODS: Patients with PROC were randomized to receive single-agent chemotherapy with or without bevacizumab. PD by CA-125 was defined according to GCIG criteria (except that confirmatory CA-125 measurement was not required). This exploratory analysis included patients with RECIST PD and a CA-125 reading ≤28 days before and ≤21 days after RECIST-defined PD. RESULTS: Of 218 eligible patients, only 94 (43%, 95% confidence interval 36% to 50%) had concordant RECIST and CA-125 PD status (42% in the chemotherapy-alone arm; 45% in the bevacizumab combination arm, P = 0.6). There was no evidence of CA-125-defined PD in the remaining 124 patients despite PD according to imaging. There were no significant differences in baseline characteristics between patients with PD defined by both RECIST and CA-125 and those with RECIST-only PD. CA-125 was even less sensitive in detecting PD in patients with early (<8 weeks after randomization) compared with later RECIST-defined PD (69% versus 53%, respectively, not meeting CA-125 criteria; P = 0.053). There was no significant difference in survival after PD in patients with concordant PD by RECIST and CA-125 versus those with PD only by RECIST. We validated our findings in an independent study population of PROC. CONCLUSIONS: In this platinum-resistant population, PD was typically detected earlier by imaging than by CA-125, irrespective of bevacizumab treatment. Disease status by CA-125 at the time of PD was not prognostic for overall survival. Regular radiologic assessment as well as symptom benefit assessment should be considered during PROC follow-up.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno Ca-125/genética , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Bevacizumab/uso terapéutico , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/epidemiología , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Platino (Metal)/uso terapéutico , Pronóstico , Criterios de Evaluación de Respuesta en Tumores SólidosRESUMEN
BACKGROUND: Progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes (PROs) were significantly improved by adding bevacizumab to chemotherapy for platinum-resistant ovarian cancer (PROC) in the phase III AURELIA trial. We explored treatment outcomes according to primary platinum resistance (PPR) versus secondary platinum resistance (SPR). PATIENTS AND METHODS: Patients were categorized as PPR (disease progression <6 months after completing first-line platinum therapy) or SPR (progression ≥6 months after first platinum but <6 months after second). The exploratory Cox and logistic regression analyses correlated PFS, ORR, overall survival (OS), and PROs with the time to development of platinum resistance. RESULTS: Baseline characteristics were similar in patients with PPR (n = 262; 73%) and SPR (n = 99; 27%), although ascites were more common in the PPR subgroup. In bevacizumab-treated patients (n = 179), SPR was associated with improved PFS (median 10.2 versus 5.6 months in PPR patients; P < 0.001) and OS (median 22.2 versus 13.7 months, respectively; P < 0.001) but not PROs (22% versus 22% with improved abdominal/gastrointestinal symptoms at week 8/9). In multivariate analyses, SPR remained an independent prognostic factor for better PFS [adjusted hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.25-0.67; P < 0.001] and OS (HR 0.49, 95% CI 0.30-0.80; P = 0.005) in bevacizumab-treated patients, but was not statistically significant for either end point in the chemotherapy-alone subgroup. The magnitude of PFS benefit from bevacizumab appeared greater in SPR than PPR patients (HR 0.30 versus 0.55, respectively; interaction P = 0.07) with a similar direction of effect for OS (interaction P = 0.18). CONCLUSIONS: In bevacizumab-treated patients, PFS and OS were more favorable in SPR than PPR patients with equally improved PROs. The PFS and OS benefit from combining bevacizumab with chemotherapy was more pronounced in SPR than PPR PROC. PPR versus SPR should be a stratification factor in future trials evaluating anti-angiogenic therapy for PROC.
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Bevacizumab/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Platino (Metal)/administración & dosificación , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/efectos adversos , Supervivencia sin Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/administración & dosificación , Neoplasias Ováricas/patología , Paclitaxel/efectos adversos , Platino (Metal)/efectos adversos , Pronóstico , Resultado del TratamientoRESUMEN
The objective of this study has been to develop technologies that can reduce the content of active pharmaceutical ingredients (APIs) and bacteria from hospital wastewater. The results from the laboratory- and pilot-scale testings showed that efficient removal of the vast majority of APIs could be achieved by a membrane bioreactor (MBR) followed by ozone, ozone + hydrogen peroxide or powdered activated carbon (PAC). Chlorine dioxide (ClO(2)) was significantly less effective. MBR + PAC (450 mg/l) was the most efficient technology, while the most cost-efficient technology was MBR + ozone (156 mg O(3)/l applied over 20 min). With MBR an efficient removal of Escherichia coli and enterococci was measured, and no antibiotic resistant bacteria were detected in the effluent. With MBR + ozone and MBR + PAC also the measured effluent concentrations of APIs (e.g. ciprofloxacin, sulfamethoxazole and sulfamethizole) were below available predicted no-effect concentrations (PNEC) for the marine environment without dilution. Iodinated contrast media were also reduced significantly (80-99% for iohexol, iopromide and ioversol and 40-99% for amidotrizoateacid). A full-scale MBR treatment plant with ozone at a hospital with 900 beds is estimated to require an investment cost of 1.6 mill. and an operating cost of 1/m(3) of treated water.
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Reactores Biológicos , Desinfección/métodos , Residuos Sanitarios , Preparaciones Farmacéuticas/aislamiento & purificación , Contaminantes Químicos del Agua/aislamiento & purificación , Carbón Orgánico/química , Compuestos de Cloro/química , Peróxido de Hidrógeno/química , Óxidos/química , Ozono/química , Aguas ResidualesRESUMEN
BACKGROUND: Patients with platinum-sensitive recurrent ovarian cancer have variable prognosis and survival. We extend previous work on prediction of progression-free survival by developing a nomogram to predict overall survival (OS) in these patients treated with platinum-based chemotherapy. PATIENTS AND METHODS: The nomogram was developed using data from the CAELYX in Platinum-Sensitive Ovarian Patients (CALYPSO) trial. Multivariate proportional hazards models were generated based on pre-treatment characteristics to develop a nomogram that classifies patient prognosis based on OS outcome. We also developed two simpler models with fewer variables and conducted model validations in independent datasets from AGO-OVAR Study 2.5 and ICON 4. We compare the performance of the nomogram with the simpler models by examining the differences in the C-statistics and net reclassification index (NRI). RESULTS: The nomogram included six significant predictors: interval from last platinum chemotherapy, performance status, size of the largest tumour, CA-125, haemoglobin and the number of organ sites of metastasis (C-statistic 0.67; 95% confidence interval 0.65-0.69). Among the CALPYSO patients, the median OS for good, intermediate and poor prognosis groups was 56.2, 31.0 and 20.8 months, respectively. When CA-125 was not included in the model, the C-statistics were 0.65 (CALYPSO) and 0.64 (AGO-OVAR 2.5). A simpler model (interval from last platinum chemotherapy, performance status and CA-125) produced a significant decrease of the C-statistic (0.63) and NRI (26.4%, P < 0.0001). CONCLUSIONS: This nomogram with six pre-treatment characteristics improves OS prediction in patients with platinum-sensitive ovarian cancer and is superior to models with fewer prognostic factors or platinum chemotherapy free interval alone. With independent validation, this nomogram could potentially be useful for improved stratification of patients in clinical trials and also for counselling patients.
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Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Platino (Metal)/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Ensayos Clínicos como Asunto , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/inducido químicamente , Recurrencia Local de Neoplasia/genética , Estadificación de Neoplasias , Nomogramas , Neoplasias Ováricas/patología , Paclitaxel/administración & dosificación , Platino (Metal)/efectos adversos , Platino (Metal)/toxicidad , Pronóstico , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
BACKGROUND: As a prelude to combination studies aimed at resistance reversal, this dose-escalation/dose-expansion study investigated the selective Src kinase inhibitor saracatinib (AZD0530) in combination with carboplatin and/or paclitaxel. METHODS: Patients with advanced solid tumours received saracatinib once-daily oral tablets in combination with either carboplatin AUC 5 every 3 weeks (q3w), paclitaxel 175 mg m(-2) q3w, paclitaxel 80 mg m(-2) every 1 week (q1w), or carboplatin AUC 5 plus paclitaxel 175 mg m(-2) q3w. The primary endpoint was safety/tolerability. RESULTS: A total of 116 patients received saracatinib 125 (N=20), 175 (N=44), 225 (N=40), 250 (N=9), or 300 mg (N=3). There were no clear dose-related trends within each chemotherapy regimen group in number or severity of adverse events (AEs). However, combining all groups, the occurrence of grade ≥3 asthenic AEs (all causality) was dose-related (125 mg, 10%; 175 mg, 20%; ≥225 mg, 33%), and grade ≥3 neutropenia occurred more commonly at doses ≥225 mg. There was no evidence that saracatinib affected exposure to carboplatin or paclitaxel, or vice versa. Objective responses were seen in 5 out of 44 patients (11%) receiving carboplatin plus paclitaxel q3w, and 5 out of 24 (21%) receiving paclitaxel q1w. CONCLUSION: Saracatinib doses up to 175 mg with paclitaxel with/without carboplatin showed acceptable toxicity in most patients, and are suitable for further trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Benzodioxoles/administración & dosificación , Neoplasias/tratamiento farmacológico , Quinazolinas/administración & dosificación , Adulto , Anciano , Benzodioxoles/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Quinazolinas/efectos adversosRESUMEN
BACKGROUND: The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. PATIENTS AND METHODS: We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients). RESULTS: Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC. CONCLUSION: The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Adulto , Anciano , Carboplatino/administración & dosificación , Epirrubicina/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/fisiopatología , Paclitaxel/administración & dosificación , Cooperación del Paciente , Estudios Prospectivos , Calidad de Vida , Análisis de SupervivenciaRESUMEN
BACKGROUND: We evaluated the prognostic importance of DNA ploidy in stage I and II endometrioid adenocarcinoma (EAC) of the endometrium with a focus on DNA index. PATIENTS AND METHODS: High-resolution DNA ploidy analysis was carried out in tumor material from 937 consecutive patients with International Federation of Gynecology and Obstetrics (FIGO) stage I and II EAC of the endometrium. RESULTS: Patients with diploid (N = 728), aneuploid tumor with DNA index ≤ 1.20 (N = 118), aneuploid tumors with DNA index >1.20 (N = 39) and tetraploid tumor (N = 52) had 5-year recurrence rates 8%, 14%, 20% and 12%, respectively. Patients with aneuploid tumor with DNA index >1.20 had a poorer 5-year progression-free survival (67%) and overall survival (72%) compared with the patients with aneuploid tumor with DNA index ≤ 1.20 (81% and 89%, respectively). Aneuploid tumors with DNA index ≤ 1.20 relapsed mainly in the vagina and pelvis, whereas aneuploid tumors with DNA index >1.20 relapsed predominantly outside pelvis. CONCLUSIONS: The recurrence risk for the patients with aneuploid tumor is higher than the patients with diploid tumor in EAC of the endometrium. Based on DNA index with cut-off 1.20, aneuploid tumors can be separated into two subgroups with different recurrence pattern and survival.
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Carcinoma Endometrioide/diagnóstico , ADN de Neoplasias/genética , Neoplasias Endometriales/diagnóstico , Índice Mitótico , Ploidias , Adulto , Anciano , Anciano de 80 o más Años , Aneuploidia , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , ADN de Neoplasias/análisis , Neoplasias Endometriales/genética , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Endometrio/metabolismo , Endometrio/patología , Femenino , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Análisis de SupervivenciaRESUMEN
BACKGROUND: Pelvic radiation therapy is an important element of curative therapy for gynaecological cancers. Serious radiation-related complications developing months or years after treatment are known as late radiation tissue injury (LRTI). METHODS: We investigated the possible pain reducing effect of hyperbaric oxygen treatment (HBOT) in a study of 16 patients with LRTI after radiation for gynaecological malignancy. The 16 patients were registered prospectively, underwent HBOT for 21 consecutive days and were followed for a 6-month period after treatment using the Brief Pain Inventory, Montgomery and Aasberg Depression Rating Scale, as well as registration of global patient scores, analgesic consumption and magnetic resonance imaging (MRI) findings. RESULTS: HBOT was shown to have insignificant effect on pain, pain characteristics, daily function, the use of analgesics and MRI-related tissue injury. Fifty percent of the patients still reported some or good effect of the treatment. CONCLUSION: It is not possible to conclude from our study if gynaecological patients with pelvic pain will benefit from HBOT. The application of HBOT to selected patients may be justified, but further research with adequate sample size, as well as the timing of HBOT related to the development of LRTI, is required to establish the optimum patient selection.
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Neoplasias de los Genitales Femeninos/radioterapia , Oxigenoterapia Hiperbárica/métodos , Dolor Pélvico/terapia , Traumatismos por Radiación/terapia , Actividades Cotidianas , Analgésicos/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/efectos adversos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Dolor Pélvico/etiología , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Traumatismos por Radiación/fisiopatología , Factores de TiempoRESUMEN
BACKGROUND: The diagnosis of uterine sarcoma is associated with poor outcome for the patient and there is a need for reliable prognostic markers. Most previous studies on the prognostic value of DNA ploidy include few uterine sarcomas and report conflicting results. MATERIALS AND METHODS: We examined the prognostic value of DNA ploidy and its association with clinicopathological parameters and crude survival in a total population of 354 sarcoma. RESULTS: In univariate analyses, we observed significantly better crude survival for endometrial stromal sarcomas (ESS) and adenosarcoma (AS) patients with diploid as compared with nondiploid tumors, but not for patients with leiomyosarcomas (LMS). In Cox multivariate analyses, DNA ploidy was the only significant predictor of survival for patients with AS. In LMS, mitotic index (MI), tumor size, tumor extent and tumor margins, whereas for ESS, MI, tumor extent and tumor necrosis obtained independent significance of survival. DNA ploidy was a significant predictor of survival for LMS patients in Cox regression analyses when excluding MI. CONCLUSION: DNA ploidy might be useful as a prognostic marker in patients with LMS and AS.
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Ploidias , Sarcoma/genética , Neoplasias Uterinas/genética , Femenino , Inestabilidad Genómica , Humanos , Persona de Mediana Edad , Pronóstico , Sarcoma/patología , Análisis de Supervivencia , Neoplasias Uterinas/patologíaRESUMEN
OBJECTIVE: To describe the prevalence of chronic fatigue (CF) and associated variables in locoregional cervical cancer survivors (CCSs) surveyed > 5 years after radiotherapy. Demographic, clinical and psychological characteristics of the CCSs were compared with normative data. DESIGN: Cross-sectional study. SETTING: Department of Gynaecologic Oncology at Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. POPULATION: Seventy-nine CCSs aged < or = 79 years, treated between 1994 and 1999, representing 62% of those invited. Normative data were based on various population studies of Norwegian women. METHODS: Data were collected by means of a mailed questionnaire, which included demographic variables and instruments covering fatigue, mental distress, sexual functioning, somatic impairments and quality of life (QOL). MAIN OUTCOME MEASURES: Self-reported fatigue score and caseness of CF based on the fatigue questionnaire. RESULTS: CCSs showed 30% CF versus 13% reported in the general population (P= 0.001). CCSs with CF had a significantly lower QOL, higher levels of anxiety and depression and more physical impairments than those without CF. In a multivariable regression model, depression was the only variable significantly associated with CF in CCSs. CONCLUSIONS: More CCSs have CF than age-matched women in the general population. CF should be of clinical concern since these women also frequently have treatable mental and physical problems.
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Fatiga/etiología , Sobrevivientes , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Trastornos de Ansiedad/etiología , Estudios de Casos y Controles , Enfermedad Crónica , Estudios Transversales , Trastorno Depresivo/etiología , Femenino , Humanos , Persona de Mediana Edad , Calidad de Vida , Radioterapia/efectos adversos , Disfunciones Sexuales Fisiológicas/etiología , Encuestas y CuestionariosRESUMEN
The Gynecologic Cancer Intergroup is comprised representatives from international gynecological cancer trials organizations, which collaborate in multicenter studies to answer the clinical challenges in gynecological cancer. This review article highlights the key clinical questions facing clinical trialists over the next decade, the information and infrastructure resources available for trials, and the methods of trial development. We cover human papillomavirus (HPV)-associated neoplasia, including cervical cancer, together with endometrial cancer, ovarian cancer, and vulvar cancer. Infrastructure for clinical trials includes a database for trials, templates for protocol development, patient educational material, and financial support for clinical trials. Other critical issues include support from government and charities and government regulations.
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Ensayos Clínicos como Asunto , Neoplasias de los Genitales Femeninos/terapia , Ensayos Clínicos como Asunto/economía , Ensayos Clínicos como Asunto/instrumentación , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Femenino , Neoplasias de los Genitales Femeninos/diagnóstico , Neoplasias de los Genitales Femeninos/patología , Neoplasias de los Genitales Femeninos/prevención & control , Humanos , Metástasis de la Neoplasia , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/patología , Neoplasias Ováricas/prevención & control , Neoplasias Ováricas/terapia , Infecciones por Papillomavirus/complicaciones , Neoplasias de la Vulva/terapiaAsunto(s)
Codón/genética , Genotipo , Mutación Missense , Neoplasias Ováricas/mortalidad , Proteína p53 Supresora de Tumor/genética , Análisis Mutacional de ADN , ADN de Neoplasias/genética , ADN de Neoplasias/aislamiento & purificación , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Polimorfismo de Longitud del Fragmento de Restricción , Pronóstico , Tasa de Supervivencia , Factores de TiempoRESUMEN
AIMS: To examine the prognostic relevance of the expression of the Bcl-2, Bcl-xL, and Bax proteins in stage IB squamous cervical carcinoma (SCC). METHODS: In total, 220 patients who underwent radical hysterectomy and bilateral lymphadenectomy at the Norwegian Radium Hospital for stage IB SCC between 1987 and 1993 were studied. Immunohistochemistry using monoclonal antibodies against Bcl-2, Bcl-xL, and Bax was used to examine protein expression. Ten patients who underwent hysterectomy for uterine prolapse served as controls. RESULTS: Cytoplasmic expression of Bcl-2, Bcl-xL, and Bax was low (< 5% positive cells) in 159 of 220 (73%), 193 of 220 (87%), and 39 of 220 (18%) tumours, respectively, and high (> or = 5% positive cells) in 61 of 220 (27%), 27 of 220 (13%), and 181 of 220 (82%) tumours, respectively. In univariate analysis, all classic clinicopathological parameters but none of the investigated proteins were associated with prognosis. In multivariate analysis, only deep stromal invasion was independently related to survival. CONCLUSION: Bcl-2, Bcl-xL, and Bax were not independently associated with prognosis in stage IB SCC.
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Apoptosis , Carcinoma de Células Escamosas/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adulto , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Citoplasma/metabolismo , Femenino , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias del Cuello Uterino/patología , Proteína X Asociada a bcl-2 , Proteína bcl-XRESUMEN
We conducted the present study to evaluate the frequency and prognostic importance on long-term survival of TP53 mutations and TP53 protein accumulation in a cohort of 178 patients with early-stage ovarian carcinomas. TP53 mutations scored as aberrant temporal temperature gradient gel electrophoresis pattern from all exons were observed in 39.9% of the tumours. Full screening of exons 5-8, followed by sequencing, was successful in 135 cases, and 48 mutations altering the protein were detected in 39 cases (28.9%). TP53 mutations were slightly less common in the Federation of Gynecologists and Obstetricians stage IA than in IB/IC (P=0.05). No significant correlations with histological type, grade of differentiation, DNA ploidy status or age at diagnosis were found. TP53 protein accumulation analysed by immunohistochemistry was found in 32.6% of all tumours, and was a poor predictor of TP53 mutations with 56.4% sensitivity, 77.1% specificity, 50% positive predictive value and 81.3% negative predictive value. Neither TP53 mutations nor TP53 protein accumulation influenced the prognosis significantly in this group of patients.
Asunto(s)
Genes p53/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Proteína p53 Supresora de Tumor/genética , Anciano , Estudios de Cohortes , Análisis Mutacional de ADN , ADN de Neoplasias , Electroforesis en Gel Bidimensional , Exones , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Estadificación de Neoplasias , Ploidias , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia , Proteína p53 Supresora de Tumor/análisisRESUMEN
The objective of this study was to compare the safety and efficacy of carboplatin plus epirubicin and paclitaxel (TEC) to carboplatin and paclitaxel (TC), in the treatment of epithelial ovarian, peritoneal, or tubal carcinoma. Between March 1999 and August 2001, 887 patients were randomized to receive six to nine cycles of paclitaxel (175 mg/m2, 3 h intravenously) followed by carboplatin (AUC 5, Calvert formula) with or without epirubicin (75 mg/m2 intravenously prior to paclitaxel), on a 3-weekly schedule. The primary endpoint was progression-free survival. Demographic information: Residual disease <1 cm was reported on 41% of patients. At the end of treatment, 65% in the TEC and 55% in the TC arm had achieved a clinical complete response, and 18 and 25% a clinical partial response resulting in an overall response rate of 83% in the TEC and 80% in the TC arm, whereas 7 and 9% had progressive disease, respectively. The three-drug combination produced a markedly higher myelotoxicity, resulting in a higher frequency of febrile neutropenia (12.5% of the TEC and 1.5% of the TC patients) and a higher number of dose reductions and treatment delays. Cycle prolongation above seven days was seen in 7 and 5% of cycles in the TEC and TC arm, respectively. Stomatitis > or = grade 3 was also higher with TEC (4% TEC and 0.5% TC). Reductions in left ventricular ejection fraction of more than 15% after six courses were slightly more common with the TEC regimen (3% versus 1.5%), but the difference was not statistically significant (P = 0.2). In conclusion, treatment with the TEC combination produced a higher rate of complete responses than treatment with the TC combination. Toxicity was manageable. Long-term survival data are awaited.