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OBJECTIVES: In a prospective study of platinum-resistant ovarian cancer patients, we examined whether the Disease-related Symptoms-Physical (DRS--P) scale of the NCCN/FACT-Ovarian Cancer Symptom Index-18 (NFOSI-18) is responsive to clinical change in patients estimated by their provider to survive at least six months. METHODS: The NFOSI-18, and other FACT measures, was collected at study entry and 3 and 6 months post-enrollment. Measures were compared for those who died or dropped off study prior to 3 months or prior to 6 months (assumed as health deterioration over time), or those who stayed on study through 6 months (presumed as stable disease over time). Statistical analyses included a fitted linear mixed model for estimating the group differences over time, Cox regression to assess the probability of survival with patient-reported outcomes, and effect size. RESULTS: DRS-P scores of patients who completed only one assessment were significantly lower compared to patients who were able to complete two assessments [5.9 points lower (2.0-9.8); p < 0.01], or three assessments [8.1 points lower (4.8-11.5); p < 0.01]. Measures of abdominal discomfort, functional well-being, emotional well-being, and quality of life were also significant, but treatment side effects were not. Further, in every scale except for neurotoxicity, higher (better) baseline scores were associated with a decreased likelihood of death, after adjusting for age, performance and disease status. CONCLUSION: The NFOSI-18 DRS-P scale is responsive to clinical change. It has potential as an indicator of changing health status with ovarian cancer disease progression, distinct from treatment side effects.
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Antineoplásicos/farmacología , Neoplasias Ováricas/terapia , Medición de Resultados Informados por el Paciente , Calidad de Vida , Cuidado Terminal/métodos , Anciano , Antineoplásicos/uso terapéutico , Supervivientes de Cáncer/psicología , Supervivientes de Cáncer/estadística & datos numéricos , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/psicología , Estudios Prospectivos , Cuidado Terminal/estadística & datos numéricosRESUMEN
BACKGROUND: A dose-dense weekly schedule of paclitaxel (resulting in a greater frequency of drug delivery) plus carboplatin every 3 weeks or the addition of bevacizumab to paclitaxel and carboplatin administered every 3 weeks has shown efficacy in ovarian cancer. We proposed to determine whether dose-dense weekly paclitaxel and carboplatin would prolong progression-free survival as compared with paclitaxel and carboplatin administered every 3 weeks among patients receiving and those not receiving bevacizumab. METHODS: We prospectively stratified patients according to whether they elected to receive bevacizumab and then randomly assigned them to receive either paclitaxel, administered intravenously at a dose of 175 mg per square meter of body-surface area every 3 weeks, plus carboplatin (dose equivalent to an area under the curve [AUC] of 6) for six cycles or paclitaxel, administered weekly at a dose of 80 mg per square meter, plus carboplatin (AUC, 6) for six cycles. The primary end point was progression-free survival. RESULTS: A total of 692 patients were enrolled, 84% of whom opted to receive bevacizumab. In the intention-to-treat analysis, weekly paclitaxel was not associated with longer progression-free survival than paclitaxel administered every 3 weeks (14.7 months and 14.0 months, respectively; hazard ratio for disease progression or death, 0.89; 95% confidence interval [CI], 0.74 to 1.06; P=0.18). Among patients who did not receive bevacizumab, weekly paclitaxel was associated with progression-free survival that was 3.9 months longer than that observed with paclitaxel administered every 3 weeks (14.2 vs. 10.3 months; hazard ratio, 0.62; 95% CI, 0.40 to 0.95; P=0.03). However, among patients who received bevacizumab, weekly paclitaxel did not significantly prolong progression-free survival, as compared with paclitaxel administered every 3 weeks (14.9 months and 14.7 months, respectively; hazard ratio, 0.99; 95% CI, 0.83 to 1.20; P=0.60). A test for interaction that assessed homogeneity of the treatment effect showed a significant difference between treatment with bevacizumab and without bevacizumab (P=0.047). Patients who received weekly paclitaxel had a higher rate of grade 3 or 4 anemia than did those who received paclitaxel every 3 weeks (36% vs. 16%), as well as a higher rate of grade 2 to 4 sensory neuropathy (26% vs. 18%); however, they had a lower rate of grade 3 or 4 neutropenia (72% vs. 83%). CONCLUSIONS: Overall, weekly paclitaxel, as compared with paclitaxel administered every 3 weeks, did not prolong progression-free survival among patients with ovarian cancer. (Funded by the National Cancer Institute and Genentech; GOG-0262 ClinicalTrials.gov number, NCT01167712.).
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carboplatino/administración & dosificación , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Análisis de Intención de Tratar , Persona de Mediana EdadRESUMEN
OBJECTIVES: The goals of treating recurrent platinum-resistant ovarian cancer are palliative, aimed at reducing symptoms and improving progression free survival. A prospective trial was conducted to determine the prevalence and severity of symptoms, and associated care needs. METHODS: Eligible women included those with persistent or recurrent platinum-resistant ovarian cancer with an estimated life expectancy of at least 6â¯months. The Needs at the End-of-Life Screening Tool (NEST), FACIT-Fatigue (FACIT-F), NCCN-FACT Ovarian Symptom Index [NFOSI-18]; Disease Related Symptoms (DRS), Treatment Side Effects (TSE), and Function/Well Being (F/WB) were collected at study entry, 3 and 6â¯months. RESULTS: We enrolled 102 evaluable patients. Initiation of Do Not Resuscitate (DNR) discussions increased over time from 28% at study entry to 37% at 6â¯months. At study entry, the most common disease-related symptoms were fatigue (92%), worry (89%), and trouble sleeping (76%); 73% reported being "bothered by treatment side effects", which included nausea (41%) and hair loss (51%) neither of which changed over time. The most common NEST unmet needs were in the symptom dimension. The social dimension was associated with F/WB (pâ¯=â¯0.002) and FACIT-F (pâ¯=â¯0.006); symptoms were associated with DRS (pâ¯=â¯0.04), TSE (pâ¯=â¯0.03), and FACIT-F (pâ¯=â¯0.04); existential was not associated with any of the patient-reported symptoms; therapeutic was associated with F/WB (pâ¯=â¯0.02). CONCLUSIONS: In patients nearing the end of life, there are significant associations between disease and treatment related symptoms and unmet patient needs, which do not change substantially over time. Careful exploration of specific end-of-life care needs can improve patient-centered care and QOL.
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Neoplasias Ováricas/terapia , Calidad de Vida/psicología , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/psicologíaRESUMEN
OBJECTIVES: Predictive factors for efficacy of bevacizumab in advanced ovarian cancer have remained elusive. We investigated ascites both as a prognostic factor and as a predictor of efficacy for bevacizumab. METHODS: Using data from GOG 0218, patients receiving cytotoxic therapy plus concurrent and maintenance bevacizumab were compared to those receiving cytotoxic therapy plus placebo. The presence of ascites was determined prospectively. Chi-square and Wilcoxon-Mann-Whitney tests compared baseline variables between subgroups. Survival was estimated by Kaplan-Meier method, and Cox proportional hazard models were used to evaluate independent prognostic factors and estimate their covariate-adjusted effects on survival. RESULTS: Treatment arms were balanced with respect to ascites and other prognostic factors. Overall, 886 (80%) women had ascites, 221 (20%) did not. Those with ascites were more likely to have: poorer performance status (p<0.001); serous histology (p=0.012); higher baseline CA125 (p<0.001); and suboptimal cytoreduction (p=0.004). In multivariate survival analysis, ascites was prognostic of poor OS (Adjusted HR 1.22, 95% CI 1.00-1.48, p=0.045), but not PFS. In predictive analysis, patients without ascites treated with bevacizumab had no significant improvement in either PFS (AHR 0.81, 95% CI 0.59-1.10, p=0.18) or OS (AHR 0.94, 95% CI 0.65-1.36, p=0.76). Patients with ascites treated with bevacizumab had significantly improved PFS (AHR 0.71, 95% CI 0.62-0.81, p<0.001) and OS (AHR 0.82, 95% CI 0.70-0.96, p=0.014). CONCLUSIONS: Ascites in women with advanced ovarian cancer is prognostic of poor overall survival. Ascites may predict the population of women more likely to derive long-term benefit from bevacizumab.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ascitis/patología , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Bevacizumab/administración & dosificación , Carcinoma Epitelial de Ovario , Neoplasias de las Trompas Uterinas/patología , Neoplasias de las Trompas Uterinas/cirugía , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/cirugía , Valor Predictivo de las Pruebas , PronósticoRESUMEN
OBJECTIVE: To determine feasibility and efficacy of administering docetaxel and carboplatin chemotherapy followed by pelvic radiotherapy and then consolidation chemotherapy in patients with advanced or recurrent endometrial cancer. METHODS: Patients with surgically staged III-IV (excluding IIIA from positive cytology alone) endometrial cancer or biopsy confirmed recurrent disease were eligible. Treatment consisted of 3 cycles of docetaxel (75 mg/m²) and carboplatin (AUC 6) on a q21 day schedule followed by involved field irradiation (45 Gy)± brachytherapy and three additional cycles of docetaxel and carboplatin. Kaplan-Meier (KM) methods estimated overall survival (OS) and progression free survival (PFS). RESULTS: Forty-two patients enrolled, 7 did not complete therapy. 95% (39/41) had primary disease. Median age=58 years (range: 21-81 years). 78% (32/41)=endometrioid histology. Stages=10 IIIA, 21 IIIC, 1 IVA, 7 IVB, (recurrent=1 IC, 1 IIA). There were 23 non-hematologic and 14 grade 3 and 16 grade 4 hematologic toxicities. Seven patients died following treatment with a median follow-up of 28 months (range: 7-70 months). KM estimates and 95% confidence intervals for OS at 1 year were 95% (82-99%), at 3 years 90% (75-96%), and at 5 years 71% (45-86%). Of the 39 with primary disease, 11 progressed or died within 5 years of study enrollment. KM estimates and 95% confidence intervals for PFS at 1 year were 87% (72-94%), at 3 years 71% (51-83%), and at 5 years 64% (42-80%). CONCLUSIONS: "Sandwiching" radiation between chemotherapy for advanced or recurrent endometrial cancer merits further development based on the reported PFS and OS.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/radioterapia , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/radioterapia , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Braquiterapia/efectos adversos , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Carcinoma Endometrioide/patología , Terapia Combinada/efectos adversos , Supervivencia sin Enfermedad , Docetaxel , Fraccionamiento de la Dosis de Radiación , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Taxoides/administración & dosificación , Taxoides/efectos adversos , Adulto JovenRESUMEN
BACKGROUND: Malignant ascites often develops in advanced stages of ovarian carcinoma, consisting of single and aggregated tumor cells, or spheroids. Spheroids have commonly been used as tumor models to study drug efficacy, and have shown resistance to some chemotherapies and radiation. However, little is known about the adhesive or invasive capabilities of spheroids, and whether this particular cellular component of the ascites can contribute to dissemination of ovarian cancer. Here, we examined the invasive ability of ascites spheroids recovered from seven ovarian carcinoma patients and one primary peritoneal carcinoma (PPC) patient. METHODS: Ascites spheroids were isolated from patients, purified, and immunohistochemical analyses were performed by a pathologist to confirm diagnosis. In vitro assays were designed to quantify spheroid disaggregation on a variety of extracellular matrices and dissemination on and invasion into normal human mesothelial cell monolayers. Cell proliferation and viability were determined in each assay, and statistical significance demonstrated by the student's t-test. RESULTS: Spheroids from all of the patients' ascites samples disaggregated on extracellular matrix components, with the PPC spheroids capable of complete disaggregation on type I collagen. Additionally, all of the ascites spheroid samples adhered to and disaggregated on live human mesothelial cell monolayers, typically without invading them. However, the PPC ascites spheroids and one ovarian carcinoma ascites spheroid sample occasionally formed invasive foci in the mesothelial cell monolayers, suggestive of a more invasive phenotype. CONCLUSION: We present here in vitro assays using ascites spheroids that imitate the spread of ovarian cancer in vivo. Our results suggest that systematic studies of the ascites cellular content are necessary to understand the biology of ovarian carcinoma.
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OBJECTIVE: To estimate the effect of preoperative diagnostic hysteroscopy on peritoneal cytology in patients with endometrial cancer. METHODS: A total of 256 charts were reviewed. Two cohorts were established based on diagnosis by hysteroscopy or blind endometrial sampling via either endometrial biopsy or dilatation and curettage (D&C). Malignant or suspicious peritoneal cytology was the primary outcome. Cohorts were compared using logistic regression to correct for potential confounders of stage and grade. RESULTS: A total of 204 cases were diagnosed by endometrial biopsy or D&C, whereas 52 were identified by hysteroscopy. In the endometrial biopsy or D&C arm, 14 of 204 (6.9%) patients had malignant or suspicious cytology compared with 7 of 52 (13.5%) patients in the hysteroscopy arm (P = .15). After logistic regression controlling for stage and grade, the odds ratio for positive cytology after hysteroscopy was 3.88 (95% confidence interval 1.11,13.6; P = .03). Four of the 52 (7.7%) cases diagnosed by hysteroscopy were stage IIIA due to cytology alone compared with 3 of the 204 (1.4%) cases diagnosed by endometrial biopsy or D&C (P = .03). CONCLUSION: Hysteroscopy appears to be associated with an increased rate of malignant cytology after controlling for confounders of stage and grade. Further, there appears to be an association between hysteroscopy and upstaging patients due to cytology alone. LEVEL OF EVIDENCE: II-2.
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Neoplasias Endometriales/diagnóstico , Histeroscopía , Biopsia , Dilatación y Legrado Uterino , Neoplasias Endometriales/patología , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Oportunidad Relativa , PronósticoRESUMEN
OBJECTIVES: To evaluate the feasibility and morbidity of using saline filled tissue expanders (TE) to displace the small bowel during radiation therapy in patients with gynecologic malignancies. STUDY DESIGN: Ten patients undergoing surgical exploration for a gynecologic malignancy and deemed to be at high risk for the late effects of radiation therapy were consented for the possible placement of a TE. Indication for placement was need for post-operative radiation. Small bowel exclusion was reported in terms of the lowest loop identified on treatment planning film using orally ingested barium. RESULTS: Small bowel loops were excluded from the pelvis to varying degrees in all patients. Lowest identifiable bowel was marked at the L4-L5 interspace in one patient, L5-S1 interspace in three patients, at or near the sacral promontory in three patients, and to the middle of S2 in one patient. In two patients the TE was removed prior to simulation. Early complications included migration of the TE during treatment, development of a vesicovaginal fistula requiring immediate removal of the TE, and enterocutaneous fistula formation in a patient who developed an abscess following treatment completion. Another patient experienced a rectovaginal fistula 18 months after removal of the TE. CONCLUSIONS: TE placement can successfully isolate small bowel from the pelvis. Usage should be individualized to minimize the likelihood of short and long-term complications, particularly in patients at higher risk of morbidity.
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Neoplasias de los Genitales Femeninos/radioterapia , Intestino Delgado/lesiones , Intestino Delgado/efectos de la radiación , Traumatismos por Radiación/prevención & control , Radioterapia/efectos adversos , Cloruro de Sodio , Dispositivos de Expansión Tisular , Adulto , Anciano , Relación Dosis-Respuesta en la Radiación , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/cirugía , Estudios de Factibilidad , Femenino , Neoplasias de los Genitales Femeninos/cirugía , Humanos , Persona de Mediana Edad , Dispositivos de Expansión Tisular/efectos adversos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugíaRESUMEN
BACKGROUND: Thalidomide is an antiangiogenic agent with immune modulating potential. The objective of this study was to determine response rates among women who were treated for recurrent ovarian cancer using topotecan with or without thalidomide. METHODS: Women were enrolled in this multicenter, prospective, randomized phase 2 trial between April 2001 and July 2005. Eligible patients had recurrent epithelial ovarian carcinoma with measurable disease or elevated CA 125 values. Patients had received prior platinum-based chemotherapy. Treatment arms received topotecan at a dose of 1.25 mg/m(2) on Days 1 through 5 of a 21-day cycle with or without thalidomide starting at a dose of 200 mg per day and then increasing the dose as tolerated. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria. The chi-square test was used to assess differences in response and toxicity, and the log-rank test was used to compare Kaplan-Meier survival curves. RESULTS: The analysis included 69 women (39 women in the control arm and 30 women in the thalidomide arm). Known prognostic factors, including platinum sensitivity, were represented equally in each arm. The median thalidomide dose was 200 mg per day. The overall response rate in the control arm was 21% (complete response [CR] rate, 18%; partial response [PR] rate, 3%) compared with 47% in the thalidomide arm (CR rate, 30%; PR rate, 17%) (P= .03). The median progression-free survival for the control arm was 4 months compared with 6 months in the thalidomide arm (P= .02). The median overall survival was 15 months in the control arm and 19 months in the thalidomide arm (P= .67). Toxicities were similar between groups. CONCLUSIONS: The addition of thalidomide to topotecan for the treatment of recurrent ovarian cancer appears to improve response rates, and the authors believe that it warrants study through larger phase 3 trials.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Talidomida/administración & dosificación , Topotecan/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Talidomida/efectos adversos , Topotecan/administración & dosificación , Topotecan/efectos adversosRESUMEN
OBJECTIVE: The present review analyzes long-term survival, recurrence sites, and toxicity in women with peritoneal spread of endometrial treated with abdominal radiotherapy, in order to provide therapeutic options as a function of disease spread and histology. METHODS: Retrospective medical record review was performed of 86 patients receiving abdominal radiotherapy for endometrial carcinomas from 1975 to 1995 at the University of Minnesota. RESULTS: FIGO stage distribution was 54 stage IIIA, 2 stage IIIB, 11 stage IIIC, and 19 stage IVB. Disease-free survivals were 55% at 5 years, 46% at 10 years, and 36% at 20 years. Recurrence rates were 16% for stage IIIA with one peritoneal site, 48% for stage IIIA with multiple peritoneal sites or stage IIIB or stage IIIC, and 72% for stage IVB. With univariate analysis, statistical significance was found for stage, gross peritoneal disease, nodal metastases, histology, concurrent chemotherapy, isolated adnexal spread, grade, angiolymphatic invasion, myometrial invasion, and age. Multivariate analysis found only stage, histology, and age to be significant. Most recurrences were pulmonary or peritoneal. Acute toxicity was acceptable. Six percent of patients required surgical intervention for small bowel obstructions. CONCLUSIONS: Abdominal radiotherapy confers an excellent prognosis for women with stage IIIA cancers with one site of peritoneal involvement. Lack of randomized trials makes definitive treatment recommendations difficult to provide. Results are less optimal with multiple peritoneal sites of involvement, gross peritoneal spread, or papillary serous/clear cell pathology but a substantial number of such women can be cured as well.
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Neoplasias Endometriales/patología , Neoplasias Endometriales/radioterapia , Neoplasias Peritoneales/radioterapia , Neoplasias Peritoneales/secundario , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/radioterapia , Adenocarcinoma de Células Claras/secundario , Adenocarcinoma Papilar/patología , Adenocarcinoma Papilar/radioterapia , Adenocarcinoma Papilar/secundario , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/radioterapia , Cistadenocarcinoma Seroso/secundario , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Radioterapia/efectos adversos , Radioterapia/métodos , Estudios RetrospectivosRESUMEN
OBJECTIVE: The purpose of the present study is evaluation of the long-term efficacy of sequential abdominopelvic radiotherapy and melphalan in the management of ovarian carcinoma. METHODS: From 1970 to 1976, 94 women with stages I-III epithelial ovarian carcinoma enrolled in a prospective nonrandomized clinical trial were prescribed 20 Gy to the upper abdomen and 50 Gy to the pelvis followed by courses of melphalan (1 mg/kg/course). Primary endpoints were survival, recurrence, and toxicity. RESULTS: There were 19 stage I, 25 stage II, and 50 stage III patients. For all stages, overall survival was 42% at 5 years, 30% at 10 years, and 17% at 25 years. Median follow-up of the survivors was 24 years. Disease-free survival was 48% at 5 years and remained at 45% from 10 to 25 years. All but two recurrences occurred within the first 27 months. No recurrence or treatment-related death occurred after 8 years. No recurrence was salvaged. All but one initial recurrence was within the peritoneal cavity. Of the 31 patients undergoing a second-look surgical procedure, 84% were free of tumor. Only 8% of patients recurred after a negative second look. Stage and the presence of palpable postoperative disease were significant prognostic factors. Disease-free survivals were 95% from 5 to 25 years for stage I, 70% at 5 years and 60% at 25 years for stage II, and 20% from 5 to 25 years for stage III (P < 0.0001). Although no patient with postoperative palpable tumor was cured, 25% lived beyond 2 years. Stage III patients without postoperative palpable tumor achieved a 47% 25-year disease-free survival. Acute toxicity was acceptable, and 98% of patients completed radiation therapy. Chronic toxicity included a 12% small bowel obstruction rate and a 3% fatal second malignancy/hematological toxicity rate (two cases of acute myelocytic leukemia, one case of thrombocytopenia). CONCLUSIONS: The long-term disease-free survival obtained with abdominopelvic radiotherapy followed by single alkylating agent chemotherapy has not been exceeded by three subsequent decades of multiagent chemotherapy trials. Abdominal radiotherapy may be useful to consolidate complete responses following therapy multiagent chemotherapy, particularly with the upper abdominal dose escalation provided by intensity modulated radiation therapy and possibly in conjunction with chemotherapy.
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Antineoplásicos Alquilantes/uso terapéutico , Melfalán/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/efectos adversos , Terapia Combinada , Supervivencia sin Enfermedad , Células Epiteliales/patología , Femenino , Estudios de Seguimiento , Humanos , Histerectomía , Melfalán/efectos adversos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: Lymphatic and hematologic metastases are rare in microinvasive cervical cancers (FIGO stage IA1), supporting a role for conservative treatment. Cervical conization followed by prolonged surveillance is an accepted treatment in patients with low-risk features and negative surgical margins. This option is particularly appealing for younger or nulliparous patients, in whom fertility may be highly desired. CASE: We report a case of a 22-year-old, HIV-negative female with stage IA1 squamous cell cervical carcinoma who was found to have bilateral lymph node metastases in both pelvic and para-aortic distributions after electing to undergo hysterectomy. CONCLUSION: Clinicians treating patients with microinvasive cervical cancer conservatively must be aware of the possibility of lymph node involvement and should consider radiological imaging to look for metastatic disease.
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Carcinoma de Células Escamosas/patología , Ganglios Linfáticos/patología , Neoplasias del Cuello Uterino/patología , Adulto , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Histerectomía , Metástasis Linfática , Estadificación de Neoplasias , Neoplasias del Cuello Uterino/cirugíaRESUMEN
OBJECTIVES: To determine toxicity and establish a maximum tolerated dose of outpatient therapy with ifosfamide, paclitaxel, and carboplatin in women with advanced and recurrent cervical cancer. METHODS: Eligible patients had stage IVB, recurrent or persistent cervical cancer that was not amenable to curative treatment with surgery or radiation therapy. A dose escalation through four dose levels was planned. Dose limiting toxicities were defined as grade 3 or grade 4 hematologic toxicity persistent to day 1 of the next scheduled cycle, grade 2 or higher central neurologic symptoms related to ifosfamide and grade 3 or grade 4 peripheral neuropathy. RESULTS: Twelve patients, aged 29 to 71, received 64 treatments and were evaluable for toxicity. No patient was withdrawn from the study due to toxicity. Two patients had received prior radiation therapy without chemotherapy, and seven patients had received radiation therapy with concurrent chemotherapy. No dose limiting toxicity occurred at dose levels 1 or 2. Three dose reductions occurred at dose level 3 due to neutropenia and thrombocytopenia. The maximum tolerated dose is ifosfamide 2 g/m(2) over 2 h, paclitaxel 175 mg/m(2) over 1 h, and carboplatin at an AUC of 5 over 45 min. Grade 3 or grade 4 neutropenia was seen in 11 subjects. Two patients required growth factor support. Grade 3 or grade 4 anemia was seen in one patient. Grade 3 or grade 4 neuropathy was seen in one patient. Other grade 3 or grade 4 non-hematologic toxicity included muscle weakness, myalgia, cough, and shortness of breath. CONCLUSIONS: Combination therapy with ifosfamide 2 g/m(2), paclitaxel 175 mg/m(2), carboplatin AUC = 5 appears to be a safe regimen for the outpatient treatment of women with advanced or recurrent cervical cancer and warrants phase II investigation.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Adulto , Anciano , Atención Ambulatoria , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Ifosfamida/administración & dosificación , Ifosfamida/efectos adversos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversosRESUMEN
OBJECTIVES: To assess the antitumor activity of Temozolomide, a novel alkylating agent, in patients with persistent or recurrent ovarian or primary peritoneal carcinoma who have failed other second-line chemotherapy agents. To identify the nature and degree of toxicity of Temozolomide in this group of patients. METHODS: Temozolomide was administered orally at an initial dose of 150 mg/m(2) daily for 5 days, every 4 weeks. If the initial course was tolerated without dose-limiting toxicity, then the dose was increased to 200 mg/m(2). Patients were evaluated for response and toxicity. RESULTS: Fifteen patients were enrolled and evaluated. The median number of prior treatment regimens was 3. Hematologic toxicity was encountered in 26% of patients and was manageable. There were no complete or partial responses. One patient had stable disease with significant improvement in her performance status while on treatment. CONCLUSION: This dose and schedule of Temozolomide had insignificant activity in this heavily pretreated group of patients with persistent or recurrent ovarian or primary peritoneal carcinoma.
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Antineoplásicos Alquilantes/uso terapéutico , Dacarbazina/análogos & derivados , Dacarbazina/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos Alquilantes/efectos adversos , Dacarbazina/efectos adversos , Esquema de Medicación , Células Epiteliales/patología , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/patología , TemozolomidaRESUMEN
INTRODUCTION: Endometrial stromal sarcomas (ESS) are a rare gynecologic malignancy. The optimal management of this cancer remains unclear, although previous reports have failed to demonstrate a clear benefit to adjuvant chemotherapy or radiation. With the successful application of directed biological therapy in other sarcomas, a review of the behavior and biology of this disease is warranted. OBJECTIVES: To review outcomes and patterns of failure in patients with endometrial stromal sarcoma diagnosed over 31 years at our institution and the relationship to protooncogene c-kit expression. MATERIALS AND METHODS: Hospital records and pathology were reviewed for 28 patients with endometrial stromal sarcomas [19 low-grade (LGESS) and 9 high-grade (HGESS)] treated between 1972 and 2003. Archival tissue samples from 16 patients were available and stained with CD 117 (c-kit) antibody (1:25 dilution). Staining intensity was graded 1+ to 3+ and distribution of the cellular staining as focal (10-30% of the cells), intermediate (30-60% of the cells), or diffuse (>60% of the cells). Positive tumors had more than 10% of cells comprising the neoplasm display immunoreactivity. RESULTS.: We found a significant difference in 5-year overall survival between LGESS and HGESS (P = 0.001). There was no significant difference in overall survival for patients with local versus advanced disease (P = 0.53) or in overall survival for those who underwent lymphadenectomy and those who did not (P = 0.92). 50% of patients received postoperative radiation with no difference in disease-free or overall survival (P = 0.68 and P = 0.53). Ten patients relapsed (36%, four HGESS and six LGESS). Seven of sixteen (43.8%) tumor samples expressed detectable c-kit. Five of seven (71%) were HGESS, and the other two (22%) were LGESS tumors. The median survival of patients with c-kit-positive versus c-kit-negative tumors was 12 and 47 months, respectively. CONCLUSIONS: This study confirms the superior overall prognosis of LGESS relative to HGESS, despite the similar rates of relapse. Although hard to assess, due to population heterogeneity and small numbers, adjuvant chemotherapy and radiation appear to be of limited benefit. Expression of c-kit was common, especially in high-grade lesions and may represent a potential therapeutic target.
Asunto(s)
Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/terapia , Recurrencia Local de Neoplasia/metabolismo , Proteínas Proto-Oncogénicas c-kit/biosíntesis , Sarcoma Estromático Endometrial/metabolismo , Sarcoma Estromático Endometrial/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Humanos , Histerectomía , Escisión del Ganglio Linfático , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Radioterapia Adyuvante , Estudios Retrospectivos , Sarcoma Estromático Endometrial/patología , Resultado del TratamientoRESUMEN
OBJECTIVES: Studies in several solid tumors have shown that the presence of occult metastasis in the bone marrow or peripheral blood is highly predictive of decreased disease-free and overall survival. Our objective was to determine the incidence of circulating ovarian or primary peritoneal cancer cells in the peripheral blood at the time of disease diagnosis, or recurrence, and to determine the prognostic significance of these occult metastasis. METHODS: Peripheral blood was drawn preoperatively from 91 women thought to have newly diagnosed or recurrent epithelial ovarian or primary peritoneal carcinoma. All samples underwent a tumor-enriched immunocytochemical assay. RESULTS: Sixty-four women were found to have epithelial ovarian or primary peritoneal cancer. Of the 64 women with cancer, 12 had evidence of circulating cancer cells in their peripheral blood (18.7%). Characteristics were compared between those with circulating cancer cells and those without, using Fisher's exact test or the Wilcoxon-Mann-Whitney test, as appropriate. Women with circulating cancer cells had statistically more grade 3 tumors than women without. At a mean follow-up of 18.7 months (SD 6.7 months), analysis using Kaplan-Meier estimation and the log-rank test indicated that survival curves did not differ between patients with and without circulating cancer cells. CONCLUSIONS: Ovarian and primary peritoneal cancer, which historically has been thought to spread primarily by direct cell seeding throughout the abdominal cavity, can have circulating cancer cells in the peripheral blood. The clinical utility of identifying circulating cancer cells is yet to be defined.
Asunto(s)
Células Neoplásicas Circulantes/patología , Neoplasias Ováricas/sangre , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/sangre , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Cuidados Preoperatorios , PronósticoRESUMEN
OBJECTIVES: Based on the reduced morbidity seen in our retrospective study, we undertook a prospective, randomized trial to determine whether transposition of the sartorius muscle improves post-operative morbidity in women with squamous cell carcinoma of the vulva undergoing inguinal-femoral lymphadenectomy. METHODS: Patients with squamous carcinoma of the vulva requiring inguinal-femoral lymphadenectomy were randomized to undergo sartorius transposition or not. All patients received perioperative antibiotics, DVT prophylaxis, and closed suction surgical site drainage. Outcomes assessed include wound cellulitis, wound breakdown, lymphocyst formation, lymphedema, and/or rehospitalization. Cohorts were compared using Fisher's exact test. Baseline characteristics were compared using Student's t test or Fischer's exact test as appropriate. Logistic regression was used to assess the impact of sartorius transposition, after adjusting for other factors. RESULTS: From June 1996 to December 2002, 61 patients underwent 99 inguinal-femoral lymphadenectomies, 28 with sartorius transposition, and 33 without. The mean (SD) age for controls and patients undergoing sartorius transposition was 63.5 (15.2) and 73.8 (13.7) years, respectively (P < 0.05). There were no statistically significant differences in BSA, tobacco use, co-morbid medical conditions, past surgical history, medication use, size of incision, duration of surgery, number of positive lymph nodes, pathologic stage, pathologic grade, pre- or postoperative hemoglobin, or length of hospitalization. There were no statistically significant differences in the incidence of wound cellulitis, wound breakdown, lymphedema, or rehospitalization. The incidence of lymphocyst formation was increased in the sartorius transposition group. After adjusting for age, however, the groups appeared similar. CONCLUSIONS: Sartorius transposition after inguinal-femoral lymphadenectomy does not reduce postoperative wound morbidity.