RESUMO
OBJECTIVE: To assess patient-reported health-related quality of life (HRQoL) in patients with ovarian cancer (OC) who received niraparib as first-line maintenance therapy. METHODS: PRIMA/ENGOT-OV26/GOG-3012 (NCT02655016) enrolled patients with newly diagnosed advanced OC who responded to first-line platinum-based chemotherapy. Patients were randomized (2:1) to niraparib or placebo once daily in 28-day cycles until disease progression, intolerable toxicity, or death. HRQoL was assessed as a prespecified secondary end point using patient-reported responses to the European Organisation for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30), the EORTC QLQ Ovarian Cancer Module (EORTC QLQ-OV28), the Functional Assessment of Cancer Therapy-Ovarian Symptom Index (FOSI), and EQ-5D-5L questionnaires. Assessments were collected at baseline and every 8 weeks (±7 days) for 56 weeks, beginning on cycle 1/day 1, then every 12 weeks (±7 days) thereafter while the patient received study treatment. RESULTS: Among trial participants (niraparib, n = 487; placebo, n = 246), PRO adherence exceeded 80% for all instruments across all cycles. Patients reported no decline over time in HRQoL measured via EORTC QLQ-C30 Global Health Status/QoL and FOSI overall scores. Scores for abdominal/gastrointestinal symptoms (EORTC QLQ-OV28) and nausea and vomiting, appetite loss, and constipation (EORTC QLQ-C30) were higher (worse symptoms) in niraparib-treated patients than placebo-treated patients; except for constipation, these differences resolved over time. Patients did not self-report any worsening from baseline of fatigue, headache, insomnia, or abdominal pain on questionnaires. CONCLUSIONS: Despite some early, largely transient increases in gastrointestinal symptoms, patients with OC treated with niraparib first-line maintenance therapy reported no worsening in overall HRQoL.
Assuntos
Indazóis , Neoplasias Ovarianas , Piperidinas , Qualidade de Vida , Humanos , Feminino , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Indazóis/uso terapêutico , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/psicologia , Idoso , Adulto , Método Duplo-Cego , Piperazinas/efeitos adversos , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Quimioterapia de Manutenção/métodos , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/administração & dosagem , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/psicologia , Idoso de 80 Anos ou maisRESUMO
OBJECTIVE: The Lifestyle Intervention for oVarian cancer Enhanced Survival (LIVES) is a national study of a combined diet and physical activity intervention for stage II-IV ovarian cancer survival, an under-represented cancer in lifestyle behavioral intervention research. Here, we present the data on recruitment, retention, and baseline demographic, clinical and lifestyle behavior characteristics of the LIVES study participants. METHODS: The LIVES study (NRG Oncology/GOG 0225) is a Phase III diet plus physical activity intervention trial testing the hypothesis that ovarian cancer survivors in the lifestyle intervention will demonstrate better progression-free survival than those in the control condition. Study interventions were delivered via centralized telephone-based health coaching. Baseline descriptive statistics were computed for demographic, clinical, and lifestyle behavior characteristics. RESULTS: The LIVES study exceeded its recruitment goals, enrolling 1205 ovarian cancer survivors from 195 NRG/NCORP-affiliated oncology practices across 49 states from 2012 to 2018. The mean age of enrollees was 59.6 years; the majority (69.4%) with stage III disease; 89% White, 5.5% Hispanic; 64% overweight/obese. Baseline self-reported diet showed a mean daily intake of 6.6 servings of fruit and vegetables, 62.7 fat grams, and 21.7 g of fiber. Physical activity averaged 13.0 MET-hours/week of moderate to vigorous physical activity; 50.9 h/week of sedentary time. Retention rates exceeded 88%. CONCLUSION: The LIVES study demonstrates efficiency in recruiting and retaining ovarian cancer survivors in a 24-month study of diet and physical activity intervention with a primary endpoint of progression free survival that will be reported. TRIAL REGISTRATION: ClinicalTrials.govNCT00719303.
Assuntos
Sobreviventes de Câncer , Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Dieta , Estilo de Vida , Exercício FísicoRESUMO
OBJECTIVE: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl). METHODS: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event. RESULTS: AUC statistics (range, 0.52-0.64) showed log(CrClJelliffe) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl <60 mL/min. Positive predictive values for adverse events ranged from 1.8%-15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively. CONCLUSION: The formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl <60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl <60 mL/min as an exclusion criterion from clinical trials.
Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Carboplatina , Creatinina , Taxa de Filtração Glomerular , Testes de Função Renal , Neoplasias Ovarianas/tratamento farmacológico , Estudos RetrospectivosRESUMO
OBJECTIVE: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction. METHODS: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included. Patients were divided into ages <70 and ≥ 70 years. Baseline characteristics, treatment compliance, toxicities, and clinical outcomes were compared. RESULTS: We included a total of 3686 patients, with 620 patients (16.8%) ≥ 70 years. OS was 37.2 months in older compared to 45.0 months in younger patients (HR 1.21, 95% CI, 1.09-1.34, p < 0.001). Older patients had an increased risk of cancer-specific-death (HR 1.16, 95% CI, 1.04-1.29) as well as non-cancer related deaths (HR 2.78, 95% CI, 2.00-3.87). Median PFS was 15.1 months in older compared to 16.0 months in younger patients (HR 1.10, 95% CI, 1.00-1.20, p = 0.056). In the carboplatin/paclitaxel arm, older patients were just as likely to complete therapy and more likely to develop grade ≥ 2 peripheral neuropathy (35.7 vs 19.7%, p < 0.001). Risk of other toxicities remained equal between groups. CONCLUSIONS: In women with advanced EOC receiving chemotherapy, age ≥ 70 was associated with shorter OS and cancer specific survival. Older patients receiving carboplatin and paclitaxel reported higher rates of grade ≥ 2 neuropathy but were not more likely to suffer from other chemotherapy related toxicities. Clintrials.gov: NCT00011986.
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Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Feminino , Humanos , Idoso , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carboplatina , Neoplasias Ovarianas/patologia , Intervalo Livre de Doença , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Paclitaxel , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estadiamento de NeoplasiasRESUMO
PURPOSE: The Sedlis criteria define risk factors for recurrence warranting post-hysterectomy radiation for early-stage cervical cancer; however, these factors were defined for squamous cell carcinoma (SCC) at an estimated recurrence risk of ≥30%. Our study evaluates and compares risk factors for recurrence for cervical SCC compared with adenocarcinoma (AC) and develops histology-specific nomograms to estimate risk of recurrence and guide adjuvant treatment. METHODS: We performed an ancillary analysis of GOG 49, 92, and 141, and included stage I patients who were surgically managed and received no neoadjuvant/adjuvant therapy. Multivariable Cox proportional hazards models were used to evaluate independent risk factors for recurrence by histology and to generate prognostic histology-specific nomograms for 3-year recurrence risk. RESULTS: We identified 715 patients with SCC and 105 with AC; 20% with SCC and 17% with AC recurred. For SCC, lymphvascular space invasion (LVSI: HR 1.58, CI 1.12-2.22), tumor size (TS ≥4 cm: HR 2.67, CI 1.67-4.29), and depth of invasion (DOI; middle 1/3, HR 4.31, CI 1.81-10.26; deep 1/3, HR 7.05, CI 2.99-16.64) were associated with recurrence. For AC, only TS ≥4 cm, was associated with recurrence (HR 4.69, CI 1.25-17.63). For both histologies, there was an interaction effect between TS and LVSI. For those with SCC, DOI was most associated with recurrence (16% risk); for AC, TS conferred a 15% risk with negative LVSI versus a 25% risk with positive LVSI. CONCLUSIONS: Current treatment standards are based on the Sedlis criteria, specifically derived from data on SCC. However, risk factors for recurrence differ for squamous cell and adenocarcinoma of the cervix. Histology-specific nomograms accurately and linearly represent risk of recurrence for both SCC and AC tumors and may provide a more contemporary and tailored tool for clinicians to base adjuvant treatment recommendations to their patients with cervical cancer.
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Recidiva Local de Neoplasia/patologia , Nomogramas , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adulto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Neoplasias do Colo do Útero/cirurgiaRESUMO
OBJECTIVES: To determine the long-term potential benefit of adjuvant chemotherapy in subgroups of high-risk stage I mucinous ovarian cancer patients using a predictive scoring algorithm. METHODS: Data were collected from the National Cancer Database from 2004 to 2014. Based on demographic and surgical characteristics, a novel 10-year survival prognostic scoring system was developed using Cox regression. RESULTS: There were 2041 eligible patients with stage I mucinous ovarian cancer including 1362 (67%) with stage IA/IB disease, 598 (29%) with stage IC disease, and 81 (4%) with stage I disease not otherwise specified. Median age was 52 with a range of 13-90 years old. 737 (36%) patients were treated with adjuvant chemotherapy. Adjuvant chemotherapy was more common in patients with stage IC relative to stage IA/IB disease (69% vs. 21%, P < 0.001) or with poorly-differentiated relative to well-differentiated tumors (69% vs. 23%, P < 0.001). Unadjusted 10-year survival was 81% relative to 79% for patients treated with vs. without chemotherapy, respectively (P = 0.46). Patients were predicted to exhibit a low- or a high-risk of death using a multivariate Cox regression model with age, stage, grade, lymphovascular space invasion and ascites. Risk of death without vs. with adjuvant chemotherapy was similar in low-risk patients (88% vs. 84%; HR = 0.80, 95%CI = 0.56-1.15, P = 0.23) and worse in high-risk patients (51% vs. 74%; HR = 1.58, 95%CI: 1.05-2.38, P = 0.03) with stage I mucinous ovarian cancer. CONCLUSIONS: A predictive scoring algorithm may provide prognostic information on long-term survival and identify high-risk stage I mucinous ovarian cancer patients who might achieve a survival benefit from adjuvant chemotherapy.
Assuntos
Adenocarcinoma Mucinoso/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Técnicas de Apoio para a Decisão , Nomogramas , Neoplasias Ovarianas/terapia , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Quimioterapia Adjuvante/estatística & dados numéricos , Tomada de Decisão Clínica/métodos , Feminino , Humanos , Histerectomia/estatística & dados numéricos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Ovário/patologia , Ovário/cirurgia , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Salpingo-Ooforectomia/estatística & dados numéricos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: Microscopic residual disease following complete cytoreduction (R0) is associated with a significant survival benefit for patients with advanced epithelial ovarian cancer (EOC). Our objective was to develop a prediction model for R0 to support surgeons in their clinical care decisions. METHODS: Demographic, pathologic, surgical, and CA125 data were collected from GOG 182 records. Patients enrolled prior to September 1, 2003 were used for the training model while those enrolled after constituted the validation data set. Univariate analysis was performed to identify significant predictors of R0 and these variables were subsequently analyzed using multivariable regression. The regression model was reduced using backward selection and predictive accuracy was quantified using area under the receiver operating characteristic area under the curve (AUC) in both the training and the validation data sets. RESULTS: Of the 3882 patients enrolled in GOG 182, 1480 had complete clinical data available for the analysis. The training data set consisted of 1007 patients (234 with R0) while the validation set was comprised of 473 patients (122 with R0). The reduced multivariable regression model demonstrated several variables predictive of R0 at cytoreduction: Disease Score (DS) (p<0.001), stage (p=0.009), CA125 (p<0.001), ascites (p<0.001), and stage-age interaction (p=0.01). Applying the prediction model to the validation data resulted in an AUC of 0.73 (0.67 to 0.78, 95% CI). Inclusion of DS enhanced the model performance to an AUC of 0.83 (0.79 to 0.88, 95% CI). CONCLUSIONS: We developed and validated a prediction model for R0 that offers improved performance over previously reported models for prediction of residual disease. The performance of the prediction model suggests additional factors (i.e. imaging, molecular profiling, etc.) should be explored in the future for a more clinically actionable tool.
Assuntos
Procedimentos Cirúrgicos de Citorredução/estatística & dados numéricos , Modelos Estatísticos , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Idoso , Antígeno Ca-125/análise , Carcinoma Epitelial do Ovário , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Proteínas de Membrana/análise , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Análise de RegressãoRESUMO
OBJECTIVE: This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC. METHODS: Patients enrolled in GOG-172 and 182 who provided specimens for translational research and consent were included. Germline DNA was evaluated with the Illumina's HumanOMNI1-Quad beadchips and scanned using Illumina's iScan optical imaging system. SNPs with allele frequency>0.05 and genotyping rate>0.98 were included. Analysis of SNPs for PFS and OS was done using Cox regression. Statistical significance was determined using Bonferroni corrected p-values with genomic control adjustment. RESULTS: The initial GWAS analysis included 1,124,677 markers in 396 patients. To obtain the final data set, quality control checks were performed and limited to serous tumors and self-identified Caucasian race. In total 636,555 SNPs and 289 patients passed all the filters. The pre-specified statistical level of significance was 7.855e-08. No SNPs met this criteria for PFS or OS, however, two SNPs were close to significance (rs10899426 p-2.144e-08) (rs6256 p-9.774e-07) for PFS and 2 different SNPs were identified (rs295315 p-7.536e-07; rs17693104 p-7.734e-07) which were close to significance for OS. CONCLUSIONS: Using the pre-specified level of significance of 1×10-08, we did not identify any SNPs of statistical significance for OS or PFS, however several were close. The SNP's identified in this GWAS study will require validation and these preliminary findings may lead to identification of novel pathways and biomarkers.
Assuntos
Cistadenocarcinoma Seroso/genética , Neoplasias Ovarianas/genética , Neoplasias Peritoneais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/patologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To determine if preoperative hypoalbuminemia is associated with postoperative wound complications among patients with vulvar cancer. METHODS: The National Surgical Quality Improvement Program database was queried for cases of vulvar cancer undergoing vulvectomy with or without lymphadenectomy (LND) from 2008 to 2013. Primary outcome was major wound complication. Secondary outcome was minor wound complication. Hypoalbuminemia was defined as albumin<3.5g/dL. Descriptive statistics and multivariable logistic regression were used for analysis. RESULTS: Of 777 vulvar cancer patients, 514 (66.2%) had vulvar surgery alone and 263 (30.3%) had a LND. Median age was 66 (range 20-90) and median BMI was 28.9kg/m(2) (range 14.3-65.5). The incidence of wound complication was 10.4% (81/777) with 48 minor and 39 major complications. There was no difference in major wound complications when a LND was performed (p=1.0). Preoperative albumin was recorded in 429 patients (55.2%). Patients with hypoalbuminemia were more likely to have a major wound complication (OR 2.9 95% CI 1.1-7.3, p=0.02), even after adjusting for BMI, age, preoperative hematocrit, and diabetes (aOR 2.7 95% CI 1.1-7.1, p=0.04). In bivariable analysis, age, diabetes, and BMI were not associated with wound complication. Patients with a wound infection had 10 times the odds of being readmitted within 30days (OR 9.5, 95% CI 4.9-18.4, p<0.01). CONCLUSIONS: Low preoperative albumin is associated with major postoperative wound complications in women undergoing surgery for vulvar cancer. When obtaining informed consent, patients with low albumin should be counseled regarding higher risks of postoperative wound complication.
Assuntos
Hipoalbuminemia/patologia , Infecção da Ferida Cirúrgica/sangue , Neoplasias Vulvares/sangue , Neoplasias Vulvares/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Hipoalbuminemia/sangue , Pessoa de Meia-Idade , Infecção da Ferida Cirúrgica/patologia , Neoplasias Vulvares/patologia , Adulto JovemRESUMO
OBJECTIVE: To estimate the probability of complete clinical response and toxicity of paclitaxel as second-line chemotherapy in measurable disease patients with malignant tumors of the ovarian stroma, and to evaluate the value of inhibin for predicting response. METHODS: Thirty-one patients with histologically confirmed ovarian stromal tumor were enrolled from 2000 to 2013. Patients were required to have measurable recurrent disease, and to have received only one prior chemotherapy regimen. Paclitaxel 175 mg/m2 was administered over a 3 hour infusion, cycling every 21 days. Inhibin levels were drawn within two weeks of initiation of treatment. RESULTS: Of 31 women enrolled, there was only one complete response (3.2%), and partial response in eight of 31 cases (25.8%). The pretreatment inhibin level for the single patient who had complete response was 88 pg/mL. Median progression-free survival was 10.0 months and overall survival was 73.6 months. Myelosuppression was common with 12 of 31 patients (38.7%) suffering grade 3 or 4 neutropenia, leukopenia, or anemia. CONCLUSION: There were too few complete responses to warrant continued evaluation of paclitaxel as a single agent treatment for women with recurrent malignant ovarian stromal tumors with measurable disease according to the primary objective of the study. Toxicity of the regimen was acceptable. Pretreatment inhibin is not a reliable tumor marker as it was not elevated in the majority of patients.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Tumores do Estroma Gonadal e dos Cordões Sexuais/tratamento farmacológico , Adulto , Antineoplásicos Fitogênicos/efeitos adversos , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/efeitos adversosRESUMO
OBJECTIVES: The aim of the study were to evaluate the gap between recommended and received adjuvant therapy in elderly patients with endometrial cancer (EC) and to determine the percent of women 70 years and older who would meet enrollment criteria for representative Gynecologic Oncology Group (GOG) trials. METHODS AND MATERIALS: An institutional review board approved retrospective chart review of all EC cases from a tertiary care institution from 2005 to 2010 was performed. Clinical, surgical, and pathologic data were abstracted from electronic medical records. Gynecologic Oncology Group protocols 249, 209, and 229L were selected as representative national EC trials. Patients were evaluated for eligibility by each protocol's criteria. RESULTS: Twenty-six percent (280/1064) of patients with EC were older than 70 years. More than 60% (181/280) of elderly patients with EC were recommended to undergo adjuvant therapy. By therapy type, 64% (48/75) of elderly patients who were recommended adjuvant radiation received it, 53% (49/92) of elderly patients who were recommended combination chemotherapy and radiation received it, and 29% (4/14) of elderly patients who were recommended chemotherapy received it. In evaluating enrollment criteria for GOG 249, 30% (40/134) of pathologically eligible patients would have been eliminated for medical clearance; for GOG 209, 31% (26/86) would have been eliminated, and for GOG 229L, 9% (4/45) would have been eliminated purely for medical reasons. CONCLUSIONS: More adjuvant treatment is recommended in the elderly patients because of a higher incidence of advanced disease and aggressive histopathology. Approximately half of the elderly patients who were recommended treatment actually received it. In addition, clinical trial data are limited for elderly patients because approximately one third of the women aged 70 years and older who meet pathologic enrollment criteria for trials were excluded because of complex medical disease.
Assuntos
Ensaios Clínicos como Assunto , Terapia Combinada/estatística & dados numéricos , Neoplasias do Endométrio/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The objective of the current study was to evaluate the effect of obesity on pretreatment quality of life (QoL) in gynecologic oncology patients. METHODS: The authors analyzed collected data from an institution-wide cohort study of women with gynecologic cancers enrolled from August 2012 to June 2013. The Functional Assessment of Cancer Therapy-General, site-specific symptom scales, and the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) global mental and physical health tools were administered. Survey results were linked to clinical data abstracted from medical records (demographics and comorbid conditions). Bivariate tests and multivariate linear regression models were used to evaluate factors associated with QoL scores. RESULTS: A total of 182 women with ovarian, uterine, cervical, and vulvar/vaginal cancers were identified; of these, 152 (84%) were assessed before surgery. Mean body mass index was 33.5 kg/m(2) and race included white (120 patients [79%]), black (22 patients [15%]), and other (10 patients [6.5%]). A total of 98 patients (64.5%) were obese (body mass index ≥30). On multivariate analysis, subscales for functional (17 vs 19; P = .04), emotional (16 vs 19; P = .008), and social (22 vs 24; P = .02) well-being as well as overall Functional Assessment of Cancer Therapy-General scores (77 vs 86; P = .002) and Patient-Reported Outcomes Measurement Information System global physical health scores (45 vs 49; P = .003) were found to be significantly lower in obese versus nonobese patients. CONCLUSIONS: Before cancer treatment, obese patients with gynecologic malignancies appear to have worse baseline QoL than their normal-weight counterparts. Emerging models of QoL-based cancer outcome measures may disproportionately affect populations with a high obesity burden. The potential disparate impact of cancer therapy on longitudinal QoL in the obese versus nonobese patients needs to be evaluated.
Assuntos
Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/cirurgia , Obesidade/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Neoplasias dos Genitais Femininos/psicologia , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/psicologia , Qualidade de Vida , Resultado do TratamentoRESUMO
PURPOSE: The aim of this study was to identify patient and physician factors related to enrollment onto Gynecologic Oncology Group (GOG) trials. METHODS: Prospective study of women with primary or recurrent cancer of the uterus or cervix treated at a GOG institution from July 2010 to January 2012. Logistic regression examined probability of availability, eligibility and enrollment in a GOG trial. Odds ratios (OR) and 95% confidence intervals (CI) for significant (p<0.05) results reported. RESULTS: Sixty institutions, 781 patients, and 150 physicians participated, 300/780 (38%) had a trial available, 290/300 had known participation status. Of these, 150 women enrolled (59.5%), 102 eligible did not enroll (35%), 38 (13%) were ineligible. Ethnicity and specialty of physician, practice type, data management availability, and patient age were significantly associated with trial availability. Patients with >4 comorbidities (OR 4.5; CI 1.7-11.8) had higher odds of trial ineligibility. Non-White patients (OR 7.9; CI 1.3-46.2) and patients of Black physicians had greater odds of enrolling (OR 56.5; CI 1.1-999.9) in a therapeutic trial. Significant patient therapeutic trial enrollment factors: belief trial may help (OR 76.9; CI 4.9->1000), concern about care if not on trial (OR12.1; CI 2.1-71.4), pressure to enroll (OR .27; CI 0.12-.64), caregiving without pay (OR 0.13; CI .02-.84). Significant physician beliefs were: patients would not do well on standard therapy (OR 3.6; CI 1.6-8.4), and trial would not be time consuming (OR 3.3; CI 1.3-8.1). CONCLUSIONS: Trial availability, patient and physician beliefs were factors identified that if modified could improve enrollment in cancer cooperative group clinical trials.
Assuntos
Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/psicologia , Seleção de Pacientes , Médicos/psicologia , Neoplasias do Colo do Útero/psicologia , Neoplasias Uterinas/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tomada de Decisões , Feminino , Humanos , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Prospectivos , Neoplasias do Colo do Útero/terapia , Neoplasias Uterinas/terapia , Adulto JovemRESUMO
BACKGROUND: The Gynecologic Oncology Group conducted this phase 2 trial to estimate the antitumor activity of bevacizumab and to determine the nature and degree of toxicity in patients with recurrent sex cord-stromal tumors of the ovary. METHODS: A prospective, multi-institutional cooperative group trial was performed in women with recurrent, measurable ovarian stromal tumors. Patients were allowed to have unlimited prior therapy, excluding bevacizumab. Bevacizumab 15 mg/kg was administered intravenously on day 1 of every 21-day cycle until patients developed disease progression or adverse effects that prohibited further treatment. The primary endpoint was the response rate (RR). Inhibin A and B levels were measured before each cycle, and the values were examined in relation to response and progression. RESULTS: Thirty-six patients were enrolled, and all were eligible and evaluable. Patients received a median of 9 cycles of treatment (range, 2-37 cycles). Six patients (16.7%) had partial responses (90% confidence interval, 7.5%-30.3%), 28 patients (77.8%) had stable disease, and 2 patients (5.6%) had progressive disease. This met the criterion for declaring the regimen active. The median progression-free survival was 9.3 months, and the median overall survival was not reached in during reporting period. Two grade 4 toxicities occurred, including hypertension and proteinuria; and the most common grade 3 toxicities were hypertension (n = 5) and pain (n = 5). Inhibin A and B values were lower in patients who responded to treatment. CONCLUSIONS: Bevacizumab has activity in the treatment of recurrent sex cord-stromal tumors of the ovary, and its toxicity is acceptable. Further investigation is warranted.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Tumores do Estroma Gonadal e dos Cordões Sexuais/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab , Feminino , Humanos , Inibinas/sangue , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/mortalidade , Estudos Prospectivos , Tumores do Estroma Gonadal e dos Cordões Sexuais/sangue , Tumores do Estroma Gonadal e dos Cordões Sexuais/mortalidadeRESUMO
OBJECTIVES: To determine the response, toxicities, and progression free survival of a regimen of temsirolimus with or without hormonal therapy in the treatment of advanced, or recurrent endometrial carcinoma. BACKGROUND: Preclinical evidence suggested that blockade of the PI3K/AKT/mTOR pathway might overcome resistance to hormonal therapy. METHODS: We performed a randomized phase II trial of intravenous temsirolimus 25mg weekly versus the combination of weekly temsirolimus with a regimen of megestrol acetate 80 mg bid for three weeks alternating with tamoxifen 20mg bid for three weeks in women with recurrent or metastatic endometrial carcinoma. RESULTS: There were 71 eligible patients who received at least one dose of therapy with 21 of these treated on the combination arm which was closed early because of an excess of venous thrombosis, with 5 episodes of deep venous thrombosis (DVT) and 2 pulmonary emboli. There were three responses observed in that arm (14%). A total of 50 eligible patients were treated on the single agent arm with 3 episodes of DVT and 11 responses (22%). Response rates were similar in patients with prior chemotherapy (7 of 29; 24%) and those with no prior chemotherapy (4 of 21; 19%). Two of four patients with clear cell carcinoma responded. CONCLUSIONS: Adding the combination of megestrol acetate and tamoxifen to temsirolimus therapy did not enhance activity and the combination was associated with an excess of venous thrombosis. Temsirolimus activity was preserved in patients with prior adjuvant chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Endométrio/tratamento farmacológico , Sirolimo/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Intervalo Livre de Doença , Esquema de Medicação , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Acetato de Megestrol/administração & dosagem , Acetato de Megestrol/efeitos adversos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversosRESUMO
OBJECTIVE: The objective of the study was to evaluate the efficacy of intravaginal application of 5% 5-fluorouracil (5-FU) for the treatment of cervical intraepithelial neoplasia (CIN) 2 in women. STUDY DESIGN: Women aged 18-29 years with CIN 2 were recruited for this randomized controlled trial of observation vs treatment with intravaginal 5-FU. Women in the observation group returned in 6 months for a Papanicolaou smear, colposcopy, and a human papillomavirus (HPV) deoxyribonucleic acid test. Women in the 5-FU group were treated with intravaginal 5-FU once every 2 weeks for a total of 16 weeks and were similarly evaluated at 6 months. All women who had a baseline visit were included in the intention-to-treat analysis. Values of P < .05 were considered statistically significant. RESULTS: Between August 2010 and June 2013, 60 women were randomized and had a baseline visit for intervention (n = 31) vs observation (n = 29). Of women who had cervical biopsy results at 6 months, regression of disease was demonstrated in 93% of women in the 5-FU group (26 of 28) and 56% of women in the observation group (15 of 27). Under the intention-to-treat analysis, a relative risk for cervical disease regression of 1.62 (95% confidence interval [CI], 1.10-2.56) was found between the 5-FU and observation arms (P = .01). When the cervical biopsy, Papanicolaou smear, and HPV results were combined for the 6 month follow-up visit, 50% of the 5-FU group (14 of 28) had a documented normal biopsy, normal Papanicolaou smear, and negative HPV test compared with 22% in the observation group (6 of 27) (relative risk, 2.25; 95% confidence interval, 1.05-5.09; P < .05). There were no moderate or severe side effects in the intervention group. CONCLUSION: Topical 5-FU appears to be an effective medical therapy for CIN 2 in young women. 5-FU is readily available and may be considered as an off-label treatment option for young women with CIN 2 who are interested in the treatment of disease but want to avoid excisional procedures.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Fluoruracila/uso terapêutico , Displasia do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/tratamento farmacológico , Administração Intravaginal , Administração Tópica , Adolescente , Adulto , Biópsia , DNA Viral/análise , Feminino , Humanos , Uso Off-Label , Teste de Papanicolaou , Papillomaviridae/genética , Estudos Prospectivos , Esfregaço Vaginal , Adulto JovemRESUMO
As nanoparticles (NPs) are cleared via phagocytes of the mononuclear phagocyte system (MPS), we hypothesized that the function of circulating monocytes and dendritic cells (MO/DC) in blood can predict NP clearance (CL). We measured MO/DC phagocytosis and reactive oxygen species (ROS) production in mice, rats, dogs, and patients with refractory solid tumors. Pharmacokinetic studies of polyethylene glycol (PEG)-encapsulated liposomal doxorubicin (PEGylated liposomal doxirubicin [PLD]), CKD-602 (S-CKD602), and cisplatin (SPI-077) were performed at the maximum tolerated dose. MO/DC function was also evaluated in patients with recurrent epithelial ovarian cancer (EOC) administered PLD. Across species, a positive association was observed between cell function and CL of PEGylated liposomes. In patients with EOC, associations were observed between PLD CL and phagocytosis (R(2) = 0.43, P = 0.04) and ROS production (R(2) = 0.61, P = 0.008) in blood MO/DC. These findings suggest that probes of MPS function may help predict PEGylated liposome CL across species and PLD CL in patients with EOC.
Assuntos
Antineoplásicos/administração & dosagem , Lipossomos/farmacologia , Sistema Fagocitário Mononuclear/efeitos dos fármacos , Adulto , Idoso , Animais , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Área Sob a Curva , Células Dendríticas/efeitos dos fármacos , Cães , Composição de Medicamentos , Feminino , Meia-Vida , Humanos , Camundongos , Pessoa de Meia-Idade , Nanopartículas , Neoplasias Ovarianas/tratamento farmacológico , Fagocitose/efeitos dos fármacos , Farmacocinética , Fenótipo , Polietilenoglicóis , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Pesquisa Translacional BiomédicaRESUMO
OBJECTIVE: The aim of this study is to report recurrence-free and overall survival for women with endometrial adenocarcinoma who were surgically staged using robotic-assisted laparoscopy. METHODS: A retrospective chart review was performed for all consecutive endometrial adenocarcinoma patients surgically staged with robotic-assisted laparoscopy at the University of North Carolina Hospital from 2005 to 2010. Demographic data, 5-year survival, and recurrence-free intervals were analyzed. Statistical analysis using Chi-square, t-test, and Kaplan-Meier curves were performed with SAS software. Study results were compared to endometrial cancer statistics from the Surveillance Epidemiology and End Results database from the National Cancer Institute. RESULTS: A total of 499 patients were identified and included in the study. Recurrence-free intervals after robotic-assisted surgical staging were 85.2% for stage IA, 80.2% for stage IB, 69.8% for stage II, and 69% for stage III. Projected 5-year survival was 88.7% for all patients included in the study. Nearly 82% of cases were endometrioid adenocarcinoma, with papillary serous, clear cell or mixed histology comprising 17.4% of cases. Median follow up time was 23 months, with a range of 0 to 80 months. Among stage IA, IB, II, and III patients, projected overall survival was 94.2%, 85.9%, 77.4%, and 68.6%, respectively. CONCLUSIONS: The results from this study demonstrate that robotic-assisted surgical staging for endometrial cancer does not adversely affect rates of recurrence or survival. These findings provide further evidence that robotic-assisted laparoscopic surgical staging is not associated with inferior results when compared to laparotomy or traditional laparoscopy.
Assuntos
Neoplasias do Endométrio/patologia , Neoplasias do Endométrio/cirurgia , Robótica/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Laparoscopia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de TempoRESUMO
OBJECTIVE: The study goal was to determine whether prior outpatient exposure to hospice discussion altered the inpatient course and end-of-life (EOL) care among patients ultimately discharged to hospice. METHODS: Medical records from January 2009 to June 2012 were reviewed and data were abstracted under an IRB-approved protocol. Hospice discussions were identified in the last outpatient clinical encounter prior to admission. Kaplan-Meier was used to estimate overall survival (OS) and the log-rank test was used to test for differences. RESULTS: There were 89 hospitalizations resulting in discharge to hospice care: 41 women with ovarian (46%), 23 with uterine (29%), 19 with cervical (21.3%), and with 6 vulvar/vaginal (6.7%) cancers. 83 patients (93%) had outpatient clinical encounters prior to admission;18% (15/83) were exposed to a hospice discussion (HD) and 82% (68/83) were not (NHD). Median time from last outpatient encounter was 18 days (range 0-371). NHD patients had longer inpatient length of stay (median 7 days vs. 4 days, p=0.008) and were less likely to receive palliative care consults than the HD patients (65% vs. 93%, p=0.03). Median OS for HD patients was 33 days (95% CI 22d-61 d) vs. 60 days (95% CI 49 d-84 d) for NHD patients (p=0.01). There were no differences detected based on race, ethnicity, or insurance status. CONCLUSIONS: HD patients had significantly shorter OS suggesting that providers were accurate in identifying patients nearing the EOL. Patients exposed to outpatient hospice discussions had a shorter length of stay and increased utilization of palliative care resources.
Assuntos
Neoplasias dos Genitais Femininos/psicologia , Neoplasias dos Genitais Femininos/terapia , Hospitais para Doentes Terminais/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Assistência Terminal/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais para Doentes Terminais/métodos , Humanos , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Modelos de Riscos Proporcionais , Análise de Regressão , Assistência Terminal/métodos , Assistência Terminal/psicologiaRESUMO
OBJECTIVE: To determine the radiographic characteristics of ovarian granulosa cell tumors (GCTs) and to evaluate the use of CA125 levels >35 in combination with imaging as an algorithm for preoperative diagnosis. METHODS: A retrospective analysis of women from two academic medical centers who were diagnosed with ovarian GCT between January 1998 and August 2012 was conducted. Clinical data included tumor appearance on pre-operative imaging and CA125 levels. Ovarian cysts were defined as complex if imaging exhibited multicystic areas, hemorrhagic, solid, or cystic and solid components. A CA125 level >35 was abnormal. RESULTS: One hundred and fifteen women were diagnosed with GCTs, of whom 63 underwent pre-operative imaging. Median age at surgery was 46 years (12-87). Forty women had preoperative ultrasounds, 43 had CT scans and 20 underwent both modalities. GCTs were almost exclusively classified as complex cysts in 62 (98%) cases. The most common morphology was solid and cystic (n=44 (70%)). Forty-four (70%) patients had tumors >10 cm. Forty-two patients had a pre-operative CA125 performed. Eighteen (43%) patients had complex masses and CA125 >35. Twenty-three (55%) had CA125 <35 with a complex mass, and one (2%) had a unilocular cyst with a CA125 >35. CONCLUSIONS: In this study, there was a near equal distribution of patients with complex masses and CA125 levels > or <35. If established strategies to predict malignancy are applied to GCTs, we will frequently fail to make the diagnosis pre-operatively. Additional research is necessary to generate an appropriate algorithm to guide pre-operative referral to a gynecologic oncologist.