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1.
Gynecol Oncol Rep ; 52: 101353, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38571566

RESUMEN

Sertoli-Leydig cell tumors (SLCT) are a rare form of sex cord stromal tumors. DICER1 germline mutations have been identified in a portion of these cases. We report a 15-year-old individual who presented to a well-child visit with secondary amenorrhea and subjective observations of a deepening voice and broadening shoulders. Elevations were noted in serum testosterone, inhibin B, androstenedione, and DHEA. Pelvic ultrasound and magnetic resonance imaging (MRI) revealed a left ovarian complex lesion measuring 5.8 x 5.5 x 4.6 cm. A laparoscopic unilateral salpingo-oophorectomy was performed with negative pelvic washings and a diagnosis of stage 1A, poorly differentiated/grade 3 SLCT of the ovary. Somatic and germline testing both demonstrated DICER1 pathologic variations. Adjuvant chemotherapy with cisplatin/etoposide/ifosfamide (PEI) was completed under the care of pediatric oncology, and this patient is now undergoing surveillance with no signs of recurrence. DICER1 Syndrome is associated with multiple tumors, including SLCT, pleuropulmonary blastoma (PPB), cystic sarcomas, and Wilms tumor among others. Patients with SLCT found to have a DICER1 mutation should undergo genetic testing and cancer screening, which may help to identify neoplasms associated with the DICER1 mutation at an early stage. This case will serve as a useful addition to the literature and review suggested pre-operative, operative, and surveillance guidelines.

2.
Am J Obstet Gynecol ; 229(2): 93-100, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37001577

RESUMEN

The intrauterine device is one of the most effective forms of contraception. Use of the intrauterine device has increased in the United States over the last 2 decades. Two formulations are commercially available in the United States: the levonorgestrel-releasing intrauterine device and the copper intrauterine device. The levonorgestrel intrauterine device releases progestin, causing endometrial suppression and cervical mucus thickening, whereas the primary mechanism of action of the copper intrauterine device is to create a local inflammatory response to prevent fertilization. Whereas the protective effects of combined hormonal contraception against ovarian and endometrial cancer, and of tubal sterilization against ovarian cancer are generally accepted, less is known about the effects of modern intrauterine devices on the development of gynecologic malignancies. The best evidence for a protective effect of intrauterine device use against cancer incidence pertains to levonorgestrel intrauterine devices and endometrial cancer, although studies suggest that both copper intrauterine devices and levonorgestrel intrauterine devices reduce endometrial cancer risk. This is supported by the proposed dual mechanisms of action including both endometrial suppression and a local inflammatory response. Studies on the relationship between intrauterine device use and ovarian cancer risk show conflicting results, although most data suggest reduced risk of ovarian cancer in intrauterine device users. The proposed biological mechanisms of ovarian cancer reduction (foreign-body inflammatory response, increased pH, antiestrogenic effect, ovulation suppression) vary by type of intrauterine device. Whereas it has been well established that use of copper intrauterine devices confers a lower risk of cervical intraepithelial neoplasms, the effect of levonorgestrel intrauterine device use on cervical cancer remains unclear. Older studies have linked its use to a higher incidence of cervical dysplasia, but more recent literature has found a decrease in cervical cancer with intrauterine device use. Various mechanisms of protection are postulated, including device-related inflammatory response in the endocervical canal and prostaglandin-mediated immunosurveillance. Overall, the available evidence suggests that both levonorgestrel intrauterine devices and copper intrauterine devices reduce gynecologic cancer risk. Whereas there is support for the reduction of endometrial cancer risk with hormonal and copper intrauterine device use, and reduction of cervical cancer risk with copper intrauterine device use, evidence in support of risk reduction with levonorgestrel intrauterine device use for cervical and ovarian cancers is less consistent.


Asunto(s)
Anticonceptivos Femeninos , Neoplasias Endometriales , Dispositivos Intrauterinos de Cobre , Dispositivos Intrauterinos Medicados , Neoplasias Ováricas , Neoplasias del Cuello Uterino , Femenino , Humanos , Cuello del Útero , Anticonceptivos Femeninos/uso terapéutico , Neoplasias Endometriales/epidemiología , Dispositivos Intrauterinos de Cobre/efectos adversos , Dispositivos Intrauterinos Medicados/efectos adversos , Levonorgestrel/uso terapéutico , Levonorgestrel/farmacología , Neoplasias Ováricas/epidemiología , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control
3.
N Engl J Med ; 388(23): 2159-2170, 2023 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-36972022

RESUMEN

BACKGROUND: Standard first-line chemotherapy for endometrial cancer is paclitaxel plus carboplatin. The benefit of adding pembrolizumab to chemotherapy remains unclear. METHODS: In this double-blind, placebo-controlled, randomized, phase 3 trial, we assigned 816 patients with measurable disease (stage III or IVA) or stage IVB or recurrent endometrial cancer in a 1:1 ratio to receive pembrolizumab or placebo along with combination therapy with paclitaxel plus carboplatin. The administration of pembrolizumab or placebo was planned in 6 cycles every 3 weeks, followed by up to 14 maintenance cycles every 6 weeks. The patients were stratified into two cohorts according to whether they had mismatch repair-deficient (dMMR) or mismatch repair-proficient (pMMR) disease. Previous adjuvant chemotherapy was permitted if the treatment-free interval was at least 12 months. The primary outcome was progression-free survival in the two cohorts. Interim analyses were scheduled to be triggered after the occurrence of at least 84 events of death or progression in the dMMR cohort and at least 196 events in the pMMR cohort. RESULTS: In the 12-month analysis, Kaplan-Meier estimates of progression-free survival in the dMMR cohort were 74% in the pembrolizumab group and 38% in the placebo group (hazard ratio for progression or death, 0.30; 95% confidence interval [CI], 0.19 to 0.48; P<0.001), a 70% difference in relative risk. In the pMMR cohort, median progression-free survival was 13.1 months with pembrolizumab and 8.7 months with placebo (hazard ratio, 0.54; 95% CI, 0.41 to 0.71; P<0.001). Adverse events were as expected for pembrolizumab and combination chemotherapy. CONCLUSIONS: In patients with advanced or recurrent endometrial cancer, the addition of pembrolizumab to standard chemotherapy resulted in significantly longer progression-free survival than with chemotherapy alone. (Funded by the National Cancer Institute and others; NRG-GY018 ClinicalTrials.gov number, NCT03914612.).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Endometriales , Femenino , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Reparación de la Incompatibilidad de ADN , Método Doble Ciego , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos
4.
N Engl J Med ; 388(23): 2145-2158, 2023 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-36972026

RESUMEN

BACKGROUND: Dostarlimab is an immune-checkpoint inhibitor that targets the programmed cell death 1 receptor. The combination of chemotherapy and immunotherapy may have synergistic effects in the treatment of endometrial cancer. METHODS: We conducted a phase 3, global, double-blind, randomized, placebo-controlled trial. Eligible patients with primary advanced stage III or IV or first recurrent endometrial cancer were randomly assigned in a 1:1 ratio to receive either dostarlimab (500 mg) or placebo, plus carboplatin (area under the concentration-time curve, 5 mg per milliliter per minute) and paclitaxel (175 mg per square meter of body-surface area), every 3 weeks (six cycles), followed by dostarlimab (1000 mg) or placebo every 6 weeks for up to 3 years. The primary end points were progression-free survival as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, and overall survival. Safety was also assessed. RESULTS: Of the 494 patients who underwent randomization, 118 (23.9%) had mismatch repair-deficient (dMMR), microsatellite instability-high (MSI-H) tumors. In the dMMR-MSI-H population, estimated progression-free survival at 24 months was 61.4% (95% confidence interval [CI], 46.3 to 73.4) in the dostarlimab group and 15.7% (95% CI, 7.2 to 27.0) in the placebo group (hazard ratio for progression or death, 0.28; 95% CI, 0.16 to 0.50; P<0.001). In the overall population, progression-free survival at 24 months was 36.1% (95% CI, 29.3 to 42.9) in the dostarlimab group and 18.1% (95% CI, 13.0 to 23.9) in the placebo group (hazard ratio, 0.64; 95% CI, 0.51 to 0.80; P<0.001). Overall survival at 24 months was 71.3% (95% CI, 64.5 to 77.1) with dostarlimab and 56.0% (95% CI, 48.9 to 62.5) with placebo (hazard ratio for death, 0.64; 95% CI, 0.46 to 0.87). The most common adverse events that occurred or worsened during treatment were nausea (53.9% of the patients in the dostarlimab group and 45.9% of those in the placebo group), alopecia (53.5% and 50.0%), and fatigue (51.9% and 54.5%). Severe and serious adverse events were more frequent in the dostarlimab group than in the placebo group. CONCLUSIONS: Dostarlimab plus carboplatin-paclitaxel significantly increased progression-free survival among patients with primary advanced or recurrent endometrial cancer, with a substantial benefit in the dMMR-MSI-H population. (Funded by GSK; RUBY ClinicalTrials.gov number, NCT03981796.).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Endometriales , Recurrencia Local de Neoplasia , Femenino , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carboplatino/administración & dosificación , Carboplatino/efectos adversos , Reparación de la Incompatibilidad de ADN , Método Doble Ciego , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inestabilidad de Microsatélites , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/etiología , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos
5.
Gynecol Oncol ; 171: 141-150, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36898292

RESUMEN

OBJECTIVE: To determine whether a non­platinum chemotherapy doublet improves overall survival (OS) among patients with recurrent/metastatic cervical carcinoma. METHODS: Gynecologic Oncology Group protocol 240 is a phase 3, randomized, open-label, clinical trial that studied the efficacy of paclitaxel 175 mg/m2 plus topotecan 0.75 mg/m2 days 1-3 (n = 223) vs cisplatin 50 mg/m2 plus paclitaxel 135 or 175 mg/m2 (n = 229), in 452 patients with recurrent/metastatic cervical cancer. Each chemotherapy doublet was also studied with and without bevacizumab (15 mg/kg). Cycles were repeated every 21 days until progression, unacceptable toxicity, or complete response. The primary endpoints were OS and the frequency and severity of adverse effects. We report the final analysis of OS. RESULTS: At the protocol-specified final analysis, median OS was 16.3 (cisplatin-paclitaxel backbone) and 13.8 months (topotecan-paclitaxel backbone) (HR 1.12; 95% CI, 0.91-1.38; p = 0.28). Median OS for cisplatin-paclitaxel and topotecan-paclitaxel was 15 vs 12 months, respectively (HR 1.10; 95% CI,0.82-1.48; p = 0.52), and for cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab was 17.5 vs 16.2 months, respectively (HR 1.16; 95% CI, 0.86-1.56; p = 0.34). Among the 75% of patients in the study population previously exposed to platinum, median OS was 14.6 (cisplatin-paclitaxel backbone) vs 12.9 months (topotecan-paclitaxel backbone), respectively (HR 1.09; 95% CI, 0.86-1.38;p = 0.48). Post-progression survival was 7.9 (cisplatin-paclitaxel backbone) vs 8.1 months (topotecan-paclitaxel backbone) (HR 0.95; 95% CI, 0.75-1.19). Grade 4 hematologic toxicity was similar between chemotherapy backbones. CONCLUSIONS: Topotecan plus paclitaxel does not confer a survival benefit to women with recurrent/metastatic cervical cancer, even among platinum-exposed patients. Topotecan-paclitaxel should not be routinely recommended in this population. NCT00803062.


Asunto(s)
Paclitaxel , Topotecan , Neoplasias del Cuello Uterino , Análisis de Supervivencia , Topotecan/uso terapéutico , Paclitaxel/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/mortalidad , Humanos , Femenino , Cisplatino/uso terapéutico , Bevacizumab/uso terapéutico , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
6.
J Clin Oncol ; 40(13): 1464-1473, 2022 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-35130043

RESUMEN

PURPOSE: GOG-259 was a 3-arm randomized controlled trial of two web-based symptom management interventions for patients with recurrent ovarian cancer. Primary aims were to compare the efficacy of the nurse-guided (Nurse-WRITE) and self-directed (SD-WRITE) interventions to Enhanced Usual Care (EUC) in improving symptoms (burden and controllability) and quality of life (QOL). METHODS: Patients with recurrent or persistent ovarian, fallopian, or primary peritoneal cancer with 3+ symptoms were eligible for the study. Participants completed baseline (BL) surveys (symptom burden and controllability and QOL) before random assignment. WRITE interventions lasted 8 weeks to develop symptom management plans for three target symptoms. All women received EUC: monthly online symptom assessment with provider reports; online resources; and every 2-week e-mails. Outcomes were evaluated at 8 and 12 weeks after BL. Repeated-measures modeling with linear contrasts evaluated group by time effects on symptom burden, controllability, and QOL, controlling for key covariates. RESULTS: Participants (N = 497) reported mean age of 59.3 ± 9.2 years. At BL, 84% were receiving chemotherapy and reported a mean of 14.2 ± 4.9 concurrent symptoms, most commonly fatigue, constipation, and peripheral neuropathy. Symptom burden and QOL improved significantly over time (P < .001) for all three groups. A group by time interaction (P < .001) for symptom controllability was noted whereby both WRITE intervention groups had similar improvements from BL to 8 and 12 weeks, whereas EUC did not improve over time. CONCLUSION: Both WRITE Intervention groups showed significantly greater improvements in symptom controllability from BL to 8 and BL to 12 weeks compared with EUC. There were no significant differences between Nurse-WRITE and SD-WRITE. SD-WRITE has potential as a scalable intervention for a future implementation study.


Asunto(s)
Neoplasias Ováricas , Calidad de Vida , Anciano , Carcinoma Epitelial de Ovario , Fatiga , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/tratamiento farmacológico , Cuidados Paliativos , Evaluación de Síntomas
7.
Gynecol Oncol ; 160(3): 669-673, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33358492

RESUMEN

OBJECTIVE: To determine the feasibility of vaginal cuff brachytherapy (VCB) followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy (ddTC) in enriched, high-intermediate risk (H-IR) patients with early stage endometrial cancer following hysterectomy. METHODS: A phase II trial of early stage endometrial cancer patients treated with VCB (2100 cGy) followed by three cycles of carboplatin (AUC 6) and dose dense paclitaxel (80 mg/m2) weekly within 12-weeks of surgery was conducted. The primary endpoint was the proportion of patients completing both VCB and ddTC. Secondary outcomes include short and long-term toxicities, recurrence rate and sites, and progression free survival. Toxicity assessments were patient reported as well as those resulting in delays or dose modifications. RESULTS: A total of 32 evaluable patients with median age of 64.5 years were included. Most patients were endometrioid histology (18/32, 56.3%) and fully staged (21/32, 65.6%) to stage Ib (18/32, 56.3%). In total, 27/32 (84.4%) patients completed treatment per protocol. Protocol non-completion included renal insufficiency, paclitaxel reaction, and treatment refusal. Median time to VCB completion was 11 days with all patients completing three fractions of VCB. Acute toxicities with VCB included grade 1 and 2 gastrointestinal, genitourinary and fatigue symptoms. Acute toxicities associated with ddTC included infusion reaction and neutropenia. Most reported long-term toxicities were grade 1 or 2 and resolved with time. CONCLUSIONS: Treatment with VCB followed by three cycles of ddTC is well-tolerated with promising utility for treatment in enriched high-intermediate risk endometrial cancer patients. Recurrence-free and overall survival outcomes are not yet mature.


Asunto(s)
Braquiterapia/métodos , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/cirugía , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Factores de Riesgo
8.
Obstet Gynecol ; 136(5): 942-949, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33030877

RESUMEN

OBJECTIVE: To use the Messick validity framework for a simulation-based assessment of vaginal hysterectomy skills. METHODS: Video recordings of physicians at different levels of training and experience performing vaginal hysterectomy on a high-fidelity vaginal surgery model were objectively assessed using a modified 10-item Vaginal Surgical Skills Index, a one-item global scale of overall performance, and a pass-fail criterion. Participants included obstetrics and gynecology trainees and faculty from five institutions. Video recordings were independently assessed by expert surgeons blinded to the identities of the study participants. RESULTS: Fifty surgeons (11 faculty, 39 trainees) were assessed. Experience level correlated strongly with both the modified Vaginal Surgical Skills Index and global scale score, with more experienced participants receiving higher scores (Pearson r=0.81, P<.001; Pearson r=0.74, P<.001). Likewise, surgical experience was also moderately correlated with the modified Vaginal Surgical Skills Index and global scale score (Pearson r=0.55, P<.001; Pearson r=0.58, P<.001). The internal consistency of the modified Vaginal Surgical Skills Index was excellent (Cronbach's alpha=0.97). Interrater reliability of the modified Vaginal Surgical Skills Index and global scale score, as measured by the intraclass correlation coefficient, was moderate to good (0.49-0.95; 0.50-0.87). Using the receiver operating characteristic curve and the pass-fail criterion, a modified Vaginal Surgical Skills Index cutoff score of 27 was found to most accurately (area under the curve 0.951, 95% CI 0.917-0.983) differentiate competent from noncompetent surgeons. CONCLUSION: We demonstrated validity evidence for using a high-fidelity vaginal surgery model with the modified Vaginal Surgical Skills Index or global scale score to assess vaginal hysterectomy skills.


Asunto(s)
Competencia Clínica/estadística & datos numéricos , Evaluación Educacional/normas , Histerectomía Vaginal/educación , Entrenamiento Simulado , Cirujanos/estadística & datos numéricos , Adulto , Femenino , Ginecología/educación , Humanos , Masculino , Obstetricia/educación , Reproducibilidad de los Resultados , Cirujanos/educación
9.
Mol Cancer Ther ; 19(11): 2363-2370, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32847980

RESUMEN

To isolate circulating tumor cells (CTC) from women with advanced cervical cancer and estimate the impact of CTCs and treatment on overall survival and progression-free survival (PFS). A total of 7.5 mL of whole blood was drawn pre-cycle 1 and 36 days post-cycle 1 from patients enrolled on Gynecologic Oncology Group 0240, the phase III randomized trial that led directly to regulatory approval of the antiangiogenesis drug, bevacizumab, in women with recurrent/metastatic cervical cancer. CTCs (defined as anti-cytokeratin+/anti-CD45- cells) were isolated from the buffy coat layer using an anti-EpCAM antibody-conjugated ferrofluid and rare earth magnet, and counted using a semiautomated fluorescence microscope. The median pre-cycle 1 CTC count was 7 CTCs/7.5 mL whole blood (range, 0-18) and, at 36 days posttreatment, was 4 (range, 0-17). The greater the declination in CTCs between time points studied, the lower the risk of death [HR, 0.87; 95% confidence interval (CI), 0.79-0.95)]. Among patients with high (≥ median) pretreatment CTCs, bevacizumab treatment was associated with a reduction in the hazard of death (HR, 0.57; 95% CI, 0.32-1.03) and PFS (HR, 0.59; 95% CI, 0.36-0.96). This effect was not observed with low (< median) CTCs. CTCs can be isolated from women with advanced cervical cancer and may have prognostic significance. A survival benefit conferred by bevacizumab among patients with high pretreatment CTCs may reflect increased tumor neovascularization and concomitant vulnerability to VEGF inhibition. These data support studying CTC capture as a potential predictive biomarker.


Asunto(s)
Células Neoplásicas Circulantes/patología , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Manejo de la Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Terapia Molecular Dirigida , Pronóstico , Resultado del Tratamiento , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/terapia
11.
Gynecol Oncol ; 158(3): 562-569, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32641240

RESUMEN

OBJECTIVE: Women with persistent, recurrent, and/or metastatic cervical cancer have a poor prognosis. Even with the availability of cisplatin plus paclitaxel and bevacizumab, median overall survival (OS) is only 17.0 months, with median post-progression survival of approximately seven months. We studied the therapeutic vaccine, Axalimogene filolisbac (ADXS-HPV), in women who had progressed following at least one prior line of therapy (Gynecologic Oncology Group protocol 265/NCT01266460). METHODS: Volunteers ≥18 years with advanced cervical cancer and GOG performance status score of 0 or 1 were eligible for participation in this 2-stage, phase II trial. In stage 1, women received up to three doses of ADXS-HPV (1 × 109 colony-forming units in 250 mL IV over 15 min every 28 days) and were monitored for tumor progression. In stage 2, women were treated until progression, intolerable adverse events (AEs), or voluntary withdrawal of consent. Co-primary endpoints were safety and proportion of volunteers surviving ≥12 months. An estimated, combined (stages 1 + 2) 12-month OS of 35% was calculated from historical GOG cohorts to declare ADXS-HPV sufficiently active in this platinum-pre-treated population. Secondary endpoints were OS and progression-free survival (PFS). RESULTS: Among 50 evaluable volunteers, the 12-month OS was 38% (n = 19). Median OS was 6.1 months (95% CI: 4.3-12.1) and median PFS was 2.8 months (95% CI: 2.6-3.0). The most common treatment-related AEs were fatigue, chills, fever, nausea, and anemia. The majority of AEs were grade 1 or 2 and resolved spontaneously or with appropriate treatment. CONCLUSION: At the dose and schedule studied, ADXS-HPV immunotherapy was tolerable and met the protocol-specified benchmark for activity required to warrant further investigation in volunteers with cervical carcinoma.


Asunto(s)
Vacunas contra el Cáncer/administración & dosificación , Listeria monocytogenes/inmunología , Proteínas E7 de Papillomavirus/inmunología , Neoplasias del Cuello Uterino/terapia , Adulto , Anciano , Vacunas contra el Cáncer/efectos adversos , Vacunas contra el Cáncer/inmunología , Resistencia a Antineoplásicos , Femenino , Humanos , Persona de Mediana Edad , Compuestos Organoplatinos/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/inmunología
12.
Int J Gynecol Cancer ; 30(5): 596-601, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32114513

RESUMEN

INTRODUCTION: To describe patient-reported outcomes and toxicities at time of treatment discontinuation secondary to progression or toxicities in advanced/recurrent cervical cancer patients receiving chemotherapy with bevacizumab. METHODS: Summarize toxicity, grade, and health-related quality of life within 1 month of treatment discontinuation for women receiving chemotherapy with bevacizumab in GOG240. RESULTS: Of the 227 patients who received chemotherapy with bevacizumab, 148 discontinued study protocol treatment (90 for disease progression and 58 for toxicity). The median survival time from treatment discontinuation to death was 7.9 months (95% CI 5.0 to 9.0) for those who progressed versus 12.1 months (95% CI 8.9 to 23.2) for those who discontinued therapy due to toxicities. The most common grade 3 or higher toxicities included hematologic, gastrointestinal, and pain. Some 57% (84/148) of patients completed quality of life assessment within 1 month of treatment discontinuation. Those patients who discontinued treatment due to progression had a mean decline in the FACT-Cx TOI of 3.2 points versus 2.2 in patients who discontinued therapy due to toxicity. This was a 9.9 point greater decline in the FACT-Cx TOI scores than those who discontinued treatment due to progression (95% CI 2.8 to 17.0, p=0.007). The decline in quality of life was due to worsening physical and functional well-being. Those who discontinued treatment due to toxicities had worse neurotoxicity and pain. DISCUSSION: Patients who discontinued chemotherapy with bevacizumab for toxicity experienced longer post-protocol survival but significantly greater declination in quality of life than those with progression. Future trial design should include supportive care interventions that optimize physiologic function and performance status for salvage therapies.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Privación de Tratamiento , Adulto , Anciano , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Medición de Resultados Informados por el Paciente , Calidad de Vida , Topotecan/administración & dosificación , Topotecan/efectos adversos
13.
J Low Genit Tract Dis ; 23(2): 124-128, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30817687

RESUMEN

OBJECTIVE: The aim of this study is to describe risk factors associated with either false-negative cervical cancer screening or deviations from screening guidelines that result in incidentally found invasive cervical cancer at the time of simple hysterectomy for benign indications. MATERIALS AND METHODS: This is a retrospective review from 1990 to 2017 of subjects with incidental cervical cancer. Baseline demographics, preoperative evaluations, surgical data, and histopathologic characteristics were recorded. Deviations from screening guidelines or false-negative screenings were identified. Associations of independent risk factors according to age, insurance status, and histology were assessed. RESULTS: Fifty-nine subjects with a median age of 43 years were found. Abnormal uterine bleeding was the most common indication for hysterectomy (61%, n = 36) and cervical dysplasia was present in 42% (n = 25) of these cases. Of those with inappropriate screening, 38% (n = 17) did not have documented Pap test, 22% (n = 10) had Pap that was not triaged appropriately, 18% (n = 8) received Pap and colposcopy but no indicated excisional procedure, and 22% (n = 10) had an excisional procedure that was not managed according to guidelines. False-negative screening occurred in 25% subjects (n = 15). There was no significant association between age, insurance status, or histology and risk of false-negative screening or inadequate screening. CONCLUSIONS: The most common cause of incidental cervical cancer at the time of simple hysterectomy was failure to properly adhere to screening guidelines. Less frequently, false-negative screening was the cause. No independent risk factor in either group was identified in this single institutional study. Illustrated is the importance of continuing education of surgeons about adequate screening in the preoperative evaluation for benign hysterectomy.


Asunto(s)
Errores Diagnósticos/estadística & datos numéricos , Pruebas Diagnósticas de Rutina/métodos , Adhesión a Directriz , Histerectomía , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Histocitoquímica , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía
14.
Gynecol Oncol ; 148(1): 174-180, 2018 01.
Artículo en Inglés | MEDLINE | ID: mdl-29132872

RESUMEN

OBJECTIVES: The purpose of this study was to assess the prognostic significance of a simplified, clinically accessible classification system for endometrioid endometrial cancers combining Lynch syndrome screening and molecular risk stratification. METHODS: Tumors from NRG/GOG GOG210 were evaluated for mismatch repair defects (MSI, MMR IHC, and MLH1 methylation), POLE mutations, and loss of heterozygosity. TP53 was evaluated in a subset of cases. Tumors were assigned to four molecular classes. Relationships between molecular classes and clinicopathologic variables were assessed using contingency tests and Cox proportional methods. RESULTS: Molecular classification was successful for 982 tumors. Based on the NCI consensus MSI panel assessing MSI and loss of heterozygosity combined with POLE testing, 49% of tumors were classified copy number stable (CNS), 39% MMR deficient, 8% copy number altered (CNA) and 4% POLE mutant. Cancer-specific mortality occurred in 5% of patients with CNS tumors; 2.6% with POLE tumors; 7.6% with MMR deficient tumors and 19% with CNA tumors. The CNA group had worse progression-free (HR 2.31, 95%CI 1.53-3.49) and cancer-specific survival (HR 3.95; 95%CI 2.10-7.44). The POLE group had improved outcomes, but the differences were not statistically significant. CNA class remained significant for cancer-specific survival (HR 2.11; 95%CI 1.04-4.26) in multivariable analysis. The CNA molecular class was associated with TP53 mutation and expression status. CONCLUSIONS: A simple molecular classification for endometrioid endometrial cancers that can be easily combined with Lynch syndrome screening provides important prognostic information. These findings support prospective clinical validation and further studies on the predictive value of a simplified molecular classification system.


Asunto(s)
Carcinoma Endometrioide/clasificación , Carcinoma Endometrioide/genética , Neoplasias Endometriales/clasificación , Neoplasias Endometriales/genética , Carcinoma Endometrioide/patología , Reparación de la Incompatibilidad de ADN , ADN Polimerasa II/genética , Neoplasias Endometriales/patología , Femenino , Genes p53 , Humanos , Pérdida de Heterocigocidad , Inestabilidad de Microsatélites , Persona de Mediana Edad , Mutación , Proteínas de Unión a Poli-ADP-Ribosa/genética , Valor Predictivo de las Pruebas , Riesgo , Proteína p53 Supresora de Tumor/genética
15.
JAMA Oncol ; 4(2): 196-202, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29242937

RESUMEN

IMPORTANCE: Ovarian cancer is the leading cause of gynecologic cancer deaths in the United States. Pazopanib is an oral, multitarget kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptors α and ß; and proto-oncogene receptor tyrosine kinase (c-KIT). OBJECTIVE: To estimate the progression-free survival (PFS) hazard ratio (HR) of weekly paclitaxel and pazopanib compared with weekly paclitaxel and placebo in women with recurrent ovarian cancer. Secondary objectives included frequency and severity of adverse events, proportion responding, and overall survival (OS) in each arm. Translational research objectives included exploring the association between possible biomarkers and single-nucleotide polymorphisms in vascular endothelial growth factor A, interleukin 8, and hypoxia-inducible factor 1α; and PFS, OS, and proportion responding. DESIGN, SETTING, AND PARTICIPANTS: A randomized, placebo-controlled, double-blind phase 2 study was conducted at 26 participating institutions. Patients were enrolled between December 12, 2011, and April 22, 2013. Data were frozen on August 11, 2014. Participants were patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1 to 3 prior regimens and performance status of 0 to 2. One hundred six patients enrolled; 100 were evaluable for toxic effects. INTERVENTIONS: All patients received paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 every 28 days and were randomized 1:1 to pazopanib 800 mg orally daily or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was PFS. The study was designed to detect a 37.5% reduction in the hazard with 80% power (α = 10%). RESULTS: A total of 106 women (median age [range], 61 [35-87] years; 88 [83%] white) were enrolled. Study arms were well balanced for age, performance status, measurable disease, and prior bevacizumab. Proportion responding was 14 of 44 (31.8%) vs 10 of 44 (22.7%) for pazopanib plus paclitaxel vs paclitaxel alone. Median PFS was 7.5 vs 6.2 months for pazopanib plus paclitaxel vs paclitaxel alone, respectively (HR, 0.84; 90% CI, 0.57-1.22; P = .20). Median OS was 20.7 vs 23.3 months for pazopanib plus paclitaxel vs paclitaxel alone (HR, 1.04; 90% CI, 0.60-1.79; P = .90). Severe hypertension was more common on the pazopanib plus paclitaxel arm (relative risk, 12.0; 95% CI, 1.62-88.84). More patients discontinued treatment on the paclitaxel arm for disease progression (34 of 52 [65.4%] vs 17 of 54 [31.5%]), and more on the pazopanib plus paclitaxel arm for adverse events (20 of 54 [37%] vs 5 of 52 [9.6%]). No association was found between single-nucleotide polymorphisms (interleukin 8 and hypoxia-inducible factor 1α) and OS and proportion responding. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype, with 1 of 14 (7%), 3 of 15 (20%), and 4 of 8 (50%) responding, respectively. CONCLUSIONS AND RELEVANCE: The combination of pazopanib plus paclitaxel is not superior to paclitaxel in women with recurrent ovarian cancer. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01468909.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Paclitaxel/administración & dosificación , Pirimidinas/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Epitelial de Ovario/patología , Método Doble Ciego , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Humanos , Indazoles , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Neoplasias Ováricas/patología , Paclitaxel/efectos adversos , Placebos , Supervivencia sin Progresión , Proto-Oncogenes Mas , Pirimidinas/efectos adversos , Sulfonamidas/efectos adversos , Resultado del Tratamiento
16.
Lancet ; 390(10103): 1654-1663, 2017 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-28756902

RESUMEN

BACKGROUND: On Aug 14, 2014, the US Food and Drug Administration approved the antiangiogenesis drug bevacizumab for women with advanced cervical cancer on the basis of improved overall survival (OS) after the second interim analysis (in 2012) of 271 deaths in the Gynecologic Oncology Group (GOG) 240 trial. In this study, we report the prespecified final analysis of the primary objectives, OS and adverse events. METHODS: In this randomised, controlled, open-label, phase 3 trial, we recruited patients with metastatic, persistent, or recurrent cervical carcinoma from 81 centres in the USA, Canada, and Spain. Inclusion criteria included a GOG performance status score of 0 or 1; adequate renal, hepatic, and bone marrow function; adequately anticoagulated thromboembolism; a urine protein to creatinine ratio of less than 1; and measurable disease. Patients who had received chemotherapy for recurrence and those with non-healing wounds or active bleeding conditions were ineligible. We randomly allocated patients 1:1:1:1 (blocking used; block size of four) to intravenous chemotherapy of either cisplatin (50 mg/m2 on day 1 or 2) plus paclitaxel (135 mg/m2 or 175 mg/m2 on day 1) or topotecan (0·75 mg/m2 on days 1-3) plus paclitaxel (175 mg/m2 on day 1) with or without intravenous bevacizumab (15 mg/kg on day 1) in 21 day cycles until disease progression, unacceptable toxic effects, voluntary withdrawal by the patient, or complete response. We stratified randomisation by GOG performance status (0 vs 1), previous radiosensitising platinum-based chemotherapy, and disease status (recurrent or persistent vs metastatic). We gave treatment open label. Primary outcomes were OS (analysed in the intention-to-treat population) and adverse events (analysed in all patients who received treatment and submitted adverse event information), assessed at the second interim and final analysis by the masked Data and Safety Monitoring Board. The cutoff for final analysis was 450 patients with 346 deaths. This trial is registered with ClinicalTrials.gov, number NCT00803062. FINDINGS: Between April 6, 2009, and Jan 3, 2012, we enrolled 452 patients (225 [50%] in the two chemotherapy-alone groups and 227 [50%] in the two chemotherapy plus bevacizumab groups). By March 7, 2014, 348 deaths had occurred, meeting the prespecified cutoff for final analysis. The chemotherapy plus bevacizumab groups continued to show significant improvement in OS compared with the chemotherapy-alone groups: 16·8 months in the chemotherapy plus bevacizumab groups versus 13·3 months in the chemotherapy-alone groups (hazard ratio 0·77 [95% CI 0·62-0·95]; p=0·007). Final OS among patients not receiving previous pelvic radiotherapy was 24·5 months versus 16·8 months (0·64 [0·37-1·10]; p=0·11). Postprogression OS was not significantly different between the chemotherapy plus bevacizumab groups (8·4 months) and chemotherapy-alone groups (7·1 months; 0·83 [0·66-1·05]; p=0·06). Fistula (any grade) occurred in 32 (15%) of 220 patients in the chemotherapy plus bevacizumab groups (all previously irradiated) versus three (1%) of 220 in the chemotherapy-alone groups (all previously irradiated). Grade 3 fistula developed in 13 (6%) versus one (<1%). No fistulas resulted in surgical emergencies, sepsis, or death. INTERPRETATION: The benefit conferred by incorporation of bevacizumab is sustained with extended follow-up as evidenced by the overall survival curves remaining separated. After progression while receiving bevacizumab, we did not observe a negative rebound effect (ie, shorter survival after bevacizumab is stopped than after chemotherapy alone is stopped). These findings represent proof-of-concept of the efficacy and tolerability of antiangiogenesis therapy in advanced cervical cancer. FUNDING: National Cancer Institute.


Asunto(s)
Bevacizumab/efectos adversos , Bevacizumab/uso terapéutico , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/mortalidad , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Infusiones Intravenosas , Persona de Mediana Edad , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Topotecan/administración & dosificación , Topotecan/efectos adversos
17.
Gynecol Oncol ; 144(3): 459-467, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-28089376

RESUMEN

PURPOSE: A simple measure to predict chemotherapy tolerance in elderly patients would be useful. We prospectively tested the association of baseline Instrumental Activities of Daily Living (IADL) score with ability to complete 4 cycles of first line chemotherapy without dose reductions or >7days delay in elderly ovarian cancer patients. PATIENTS AND METHODS: Patients' age ≥70 along with their physicians chose between two regimens: CP (Carboplatin AUC 5, Paclitaxel 135mg/m2) or C (Carboplatin AUC 5), both given every 3weeks either after primary surgery or as neoadjuvant chemotherapy (NACT) with IADL and quality of life assessments performed at baseline, pre-cycle 3, and post-cycle 4. RESULTS: Two-hundred-twelve women were enrolled, 152 selecting CP and 60 selecting C. Those who selected CP had higher baseline IADL scores (p<0.001). After adjusting for age and PS, baseline IADL was independently associated with the choice of regimen (p=0.035). The baseline IADL score was not found to be associated with completion of 4 cycles of chemotherapy without dose reduction or delays (p=0.21), but was associated with completion of 4 cycles of chemotherapy regardless of dose reduction and delay (p=0.008) and toxicity, with the odds ratio (OR) of grade 3+ toxicity decreasing 17% (OR: 0.83; 95%CI: 0.72-0.96; p=0.013) for each additional activity in which the patient was independent. After adjustment for chemotherapy regimen, IADL was also associated with overall survival (p=0.019) for patients receiving CP. CONCLUSION: Patients with a higher baseline IADL score (more independent) were more likely to complete 4 cycles of chemotherapy and less likely to experience grade 3 or higher toxicity.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Peritoneales/tratamiento farmacológico , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias de las Trompas Uterinas/patología , Femenino , Humanos , Neoplasias Ováricas/patología , Neoplasias Peritoneales/patología
18.
J Radiol Case Rep ; 10(5): 29-35, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27761178

RESUMEN

Intravenous leiomyomatosis is a benign smooth muscle tumor which despite its histology can have devastating consequences. Furthermore, the clinical manifestations are variable and nonspecific, typically leading to delayed or missed diagnosis. Thus, it is critical for clinicians to be aware of this condition and have a high index of suspicion in a middle-aged woman with a history of uterine leiomyoma presenting with an inferior vena cava mass to enable early diagnosis and treatment. We report a case of a large intravenous leiomyoma which was initially considered to be a very large deep venous thrombosis; with thorough preoperative planning, it was successfully removed intact and in entirety with a single-stage operation.


Asunto(s)
Leiomiomatosis/diagnóstico por imagen , Músculo Liso Vascular/patología , Neoplasias Uterinas/diagnóstico por imagen , Neoplasias Vasculares/diagnóstico por imagen , Vena Cava Inferior/patología , Diagnóstico Diferencial , Femenino , Humanos , Leiomiomatosis/patología , Leiomiomatosis/cirugía , Persona de Mediana Edad , Neoplasias Uterinas/patología , Neoplasias Uterinas/cirugía , Neoplasias Vasculares/patología , Neoplasias Vasculares/cirugía
19.
J Clin Oncol ; 34(25): 3062-8, 2016 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-27325856

RESUMEN

PURPOSE: The clinicopathologic significance of mismatch repair (MMR) defects in endometrioid endometrial cancer (EEC) has not been definitively established. We undertook tumor typing to classify MMR defects to determine if MMR status is prognostic or predictive. METHODS: Primary EECs from NRG/GOG0210 patients were assessed for microsatellite instability (MSI), MLH1 methylation, and MMR protein expression. Each tumor was assigned to one of four MMR classes: normal, epigenetic defect, probable mutation (MMR defect not attributable to MLH1 methylation), or MSI-low. The relationships between MMR classes and clinicopathologic variables were assessed using contingency table tests and Cox proportional hazard models. RESULTS: A total of 1,024 tumors were assigned to MMR classes. Epigenetic and probable mutations in MMR were significantly associated with higher grade and more frequent lymphovascular space invasion. Epigenetic defects were more common in patients with higher International Federation of Gynecology and Obstetrics stage. Overall, there were no differences in outcomes. Progression-free survival was, however, worse for women whose tumors had epigenetic MMR defects compared with the MMR normal group (hazard ratio, 1.37; P < .05; 95% CI, 1.00 to 1.86). An exploratory analysis of interaction between MMR status and adjuvant therapy showed a trend toward improved progression-free survival for probable MMR mutation cases. CONCLUSION: MMR defects in EECs are associated with a number of well-established poor prognostic indicators. Women with tumors that had MMR defects were likely to have higher-grade cancers and more frequent lymphovascular space invasion. Surprisingly, outcomes in these patients were similar to patients with MMR normal tumors, suggesting that MMR defects may counteract the effects of negative prognostic factors. Altered immune surveillance of MMR-deficient tumors, and other host/tumor interactions, is likely to determine outcomes for patients with MMR-deficient tumors.


Asunto(s)
Carcinoma Endometrioide/genética , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales/genética , Carcinoma Endometrioide/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Neoplasias Endometriales/patología , Femenino , Humanos , Inestabilidad de Microsatélites , Persona de Mediana Edad , Modelos de Riesgos Proporcionales
20.
Int J Vasc Med ; 2016: 6413541, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26904290

RESUMEN

Active cancer (ACa) is strongly associated with venous thromboembolism and bleeding. Retrievable inferior vena cava filters (RIVCF) are frequently placed in these patients when anticoagulation cannot be continued. Objectives. To describe the complications and retrieval rate of inferior vena cava filters in patients with ACa. Methods. Retrospective review of 251 consecutive patients with RIVCF in a single institution. Results. We included 251 patients with RIVCF with a mean age of 58.1 years and a median follow-up of 5.4 months (164 days, IQR: 34-385). Of these patients 32% had ACa. There were no differences in recurrence rate of DVT between patients with ACa and those without ACa (13% versus 17%, p = ns). Also, there were no differences in major filter complications (11% ACa versus 7% no ACa, p = ns). The filter retrieval was not different between groups (log-rank = 0.16). Retrieval rate at 6 months was 49% in ACa patients versus 64% in patients without ACa (p = ns). Filter retrieval was less frequent in ACa patients with metastatic disease (p < 0.01) or a nonsurgical indication for filter placement (p = 0.04). Conclusions. No differences were noted in retrieval rate, recurrent DVT, or filter complications between the two groups. ACa should not preclude the use of RIVCF.

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