RESUMEN
PURPOSE: Pelvic recurrence is a frequent pattern of relapse for women with endometrial cancer. A randomized trial compared progression-free survival (PFS) after treatment with radiation therapy alone as compared with concurrent chemotherapy. MATERIALS AND METHODS: Between February 2008 and August 2020, 165 patients were randomly assigned 1:1 to receive either radiation treatment alone or a combination of chemotherapy and radiation treatment. The primary objective of this study was to determine whether chemoradiation therapy was more effective than radiation therapy alone at improving PFS. RESULTS: The majority of patients had low-grade (1 or 2) endometrioid histology (82%) and recurrences confined to the vagina (86%). External beam with either the three-dimensional or intensity modulated radiation treatment technique was followed by a boost delivered with brachytherapy or external beam. Patients randomly assigned to receive chemotherapy were treated with once weekly cisplatin (40 mg/m2). Rates of acute toxicity were higher in patients treated with chemoradiation as compared with radiation treatment alone. Median PFS was longer for patients treated with radiation therapy alone as compared with chemotherapy and radiation (median PFS was not reached for RT v 73 months for chemoradiation, hazard ratio of 1.25 (95% CI, 0.75 to 2.07). At 3 years, 73% of patients treated definitively with radiation and 62% of patients treated with chemoradiation were alive and free of disease progression. CONCLUSION: Excellent outcomes can be achieved for women with localized recurrences of endometrial cancer when treated with radiation therapy. The addition of chemotherapy does not improve PFS for patients treated with definitive radiation therapy for recurrent endometrial cancer and increases acute toxicity. Patients with low-grade and vaginal recurrences who constituted the majority of those enrolled are best treated with radiation therapy alone.
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Quimioradioterapia , Cisplatino , Neoplasias Endometriales , Recurrencia Local de Neoplasia , Humanos , Femenino , Neoplasias Endometriales/radioterapia , Neoplasias Endometriales/patología , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/terapia , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Anciano , Estudios Prospectivos , Quimioradioterapia/métodos , Supervivencia sin Progresión , Adulto , Braquiterapia/métodos , Braquiterapia/efectos adversos , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: The Targeted Agent and Profiling Utilization Registry (TAPUR) Study, a phase II basket study, evaluates anti-tumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known as drug targets. OBJECTIVE: With no known genomic targets predictive of sensitivity to cetuximab, cetuximab was evaluated in patients with breast cancer (BC), non-small cell lung cancer (NSCLC), and ovarian cancer (OC), without KRAS, NRAS, or BRAF mutations. PATIENTS AND METHODS: Eligible patients with advanced BC, NSCLC, and OC received a cetuximab loading dose, then weekly infusions (250 mg/m2 over 60 min). A Simon two-stage design, requiring ten patients in stage I, was employed per each disease-specific cohort. The primary endpoint was disease control (objective response or stable disease for at least 16 weeks). If two or more patients in stage I achieved disease control, the cohort would enroll 18 more patients in stage II. Power and alpha of the design are 85% and 10%, respectively. Secondary endpoints included progression-free survival, overall survival, and safety. RESULTS: Patients with BC (n = 10), NSCLC (n = 10), and OC (n = 29) were enrolled between June 2016 and September 2018. No objective responses or stable disease for at least 16 weeks were observed in the BC and NSCLC cohorts. No objective responses and four patients with stable disease for at least 16 weeks were observed in the OC cohort. Six of 49 patients reported grade 3 or higher adverse events or serious adverse events at least possibly related to cetuximab. CONCLUSIONS: Cetuximab does not have clinical activity in patients with advanced BC, NSCLC, and OC without KRAS, NRAS, or BRAF mutations. CLINICAL TRIAL REGISTRATION: NCT02693535 (26 February, 2016).
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Antineoplásicos Inmunológicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Cetuximab/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Anciano , Antineoplásicos Inmunológicos/farmacología , Cetuximab/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas B-raf/genética , Sistema de RegistrosRESUMEN
OBJECTIVES: Methotrexate and actinomycin-D are both effective first-line drugs for low-risk (WHO score 0-6) Gestational Trophoblastic Neoplasia (GTN) with considerable debate about which is more effective, less toxic, and better tolerated. The primary trial objective was to test if treatment with multi-day methotrexate (MTX) was inferior to pulse actinomycin-D (ACT-D). Secondary objectives included evaluation of severity and frequency of adverse events, and impact on quality of life (QOL). METHODS: This was a prospective international cooperative group randomized phase III two arm non-inferiority study (Clinical Trials Identifier: (NCT01535053). The control arm was ACT-D; the experimental arm was multi-day MTX regimen (institutional preference of 5 or 8 day). Outcome measures included complete response rate, recurrence rate, toxicity, and QOL as measured by FACT-G and FACIT supplemental items. RESULTS: The complete response rates for multi-day methotrexate and pulse actinomycin-D were 88% (23/26 patients) and 79% (22/28 patients) (p = NS) respectively, there were two recurrences in each arm, and 100% of patients survived. Significant toxicity was minimal, but mouth sores (mucositis), and eye pain were significantly more common in the MTX arm (p = 0.001 and 0.01 respectively). Quality of life showed no significant difference in overall quality of life, body image, sexual function, or treatment related side effects. The study was closed for low accrual rate (target 384, actual accrual 57), precluding statistical analysis of the primary objective. CONCLUSIONS: The complete response rate for multi-day methotrexate was higher than actinomycin-D, but did not reach statistical significance. The multi-day MTX regimens were associated with significantly more mucositis and were significantly less convenient.
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Dactinomicina/administración & dosificación , Enfermedad Trofoblástica Gestacional/tratamiento farmacológico , Metotrexato/administración & dosificación , Dactinomicina/efectos adversos , Esquema de Medicación , Femenino , Humanos , Metotrexato/efectos adversos , Medición de Resultados Informados por el Paciente , Embarazo , Calidad de VidaRESUMEN
Significant improvements in treatment and the understanding of gestational trophoblastic neoplasia have occurred in the last 15years. These diseases are almost always curable, and refractory patients have more options for salvage therapy. Recent improvements in the understanding of epidemiology, diagnosis, and cell biology have resulted in changes in staging, advances in treatment options, and opportunities for fertility preservation.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad Trofoblástica Gestacional/diagnóstico , Enfermedad Trofoblástica Gestacional/terapia , Vigilancia de la Población , Femenino , Preservación de la Fertilidad , Enfermedad Trofoblástica Gestacional/epidemiología , Enfermedad Trofoblástica Gestacional/patología , Humanos , Histerectomía , Embarazo , Terapia Recuperativa/métodosRESUMEN
BACKGROUND: Synuclein-γ (SNCG) is highly expressed in advanced solid tumors, including uterine serous carcinoma (USC). The objective of the current study was to determine whether SNCG protein was associated with survival and clinical covariates using the largest existing collection of USCs from the Gynecologic Oncology Group (GOG-8023). METHODS: High-density tissue microarrays (TMAs) of tumor tissues from 313 patients with USC were stained by immunohistochemistry for SNCG, p53, p16, FOLR1, pERK, pAKT, ER, PR, and HER2/neu. Associations of SNCG and other tumor markers with overall and progression-free survival were assessed using log-rank tests and Cox proportional-hazards models, which also were adjusted for age, race, and stage. RESULTS: The overall survival at 5 years was 46% for women with high SNCG expression and 62% for those with low SNCG expression (log-rank P = .021; hazard ratio [HR], 1.31; 95% confidence interval [CI], 0.91-1.9 in adjusted Cox model). The progression-free survival rate at 5 years was worse for women who had high SNCG expression, at 40%, compared with 56% for those who had low SNCG expression (log-rank P = .0081; HR, 1.36; 95% CI, 0.96-1.92 in adjusted Cox model). High levels of both p53 and p16 were significantly associated with worse overall survival (p53: HR, 4.20 [95% CI, 1.54-11.45]; p16: HR, 1.95 [95% CI, 1.01-3.75]) and progression-free survival (p53: HR, 2.16 [95% CI, 1.09-4.27]; p16: HR, 1.53 [95% CI, 0.87-2.69]) compared with low levels. CONCLUSIONS: This largest collection of USCs to date demonstrates that SNCG was associated with poor survival in univariate analyses. SNCG does not predict survival outcome independent of p53 and p16 in models that jointly consider multiple markers. Cancer 2017;123:1144-1155. © 2016 American Cancer Society.
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Biomarcadores de Tumor , Cistadenocarcinoma Seroso/metabolismo , Cistadenocarcinoma Seroso/mortalidad , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/mortalidad , gamma-Sinucleína/metabolismo , Anciano , Anciano de 80 o más Años , Cistadenocarcinoma Seroso/patología , Cistadenocarcinoma Seroso/terapia , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Estimación de Kaplan-Meier , Persona de Mediana Edad , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Neoplasias Uterinas/patología , Neoplasias Uterinas/terapia , gamma-Sinucleína/genéticaRESUMEN
BACKGROUND: Synuclein gamma (SNCG) expression is associated with advanced disease and chemoresistance in multiple solid tumors. Our goal was to determine if SNCG protein expression in ovarian cancer was correlated with clinicopathologic variables and patient outcomes. METHODS: Tissue microarrays from primary tumors of 357 ovarian, fallopian tube, and primary peritoneal cancer patients, who underwent primary surgery at Roswell Park Cancer Institute between 1995 and 2007, were immunohistochemically stained for SNCG. A pathologist blinded to patient data scored tumors as positive if ≥10 % of the sample stained for SNCG. Medical records were reviewed for clinicopathologic and demographic variables. Between the positive and negative groups, Wilcoxon rank-sum test was used to compare the median ages and Fisher's exact test was used to compare groups in categorical variables. Cox proportional hazard models examined associations between SNCG and overall and progression-free survival. RESULTS: The median follow-up was 36 months, median overall survival was 39 months, and median progression-free survival was 18 months. SNCG presence was associated with clinical variables of serous histology, grade 3 disease, suboptimal debulking, ascites at surgery, FIGO stage III-IV cancer, or initial CA-125 level >485. There was no significant difference in overall survival (HR 1.06 95 % CI 0.81-1.39 P 0.69) or progression-free survival (HR 1.16 95 % CI 0.89-1.50 P 0.28) for patients with or without SNCG expression. CONCLUSIONS: SNCG expression in ovarian cancer is frequent in patients with high-risk features, but it does not correlate with chemotherapy response, overall survival, or progression-free survival.
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Expresión Génica , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , gamma-Sinucleína/genética , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor , Resistencia a Antineoplásicos/genética , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/mortalidad , Pronóstico , Resultado del Tratamiento , Adulto Joven , gamma-Sinucleína/metabolismoRESUMEN
OBJECTIVE: To evaluate the efficacy and safety of second uterine curettage in lieu of chemotherapy for patients with low-risk, nonmetastatic gestational trophoblastic neoplasia (GTN) and to evaluate whether response to second curettage is independent of patient age, World Health Organization (WHO) risk score, registration human chorionic gonadotropin (hCG) level, lesion size, and depth of myometrial invasion measured on ultrasound examination. METHODS: This was a cooperative group multicenter prospective phase II study. Prestudy testing included quantitative hCG level, pelvic ultrasonography, and chest radiography. Patients were categorized according to WHO risk scoring criteria (low risk with a score of 0-6). RESULTS: Sixty-four women with newly diagnosed low-risk, nonmetastatic GTN were enrolled. Four patients were excluded. Twenty-four patients (40%) (lower 95% confidence limit 27.6%) were cured after second curettage. An additional two patients (3%) achieved a complete response but did not complete follow-up. Overall, 26 of 60 patients were able to avoid chemotherapy. Surgical failure was observed in 34 women (59%) and was more common in women 19 years old or younger or 40 years old or older. One case of grade 1 uterine perforation was successfully managed by observation. Four grade 1 and one grade 3 uterine hemorrhages were reported. New metastatic disease (lung) was identified in one of these women after second curettage. In three patients (surgical failures), the second curettage pathology was placental site trophoblastic tumor, and it was placental nodule in one additional patient. CONCLUSION: Second uterine curettage as initial treatment for low-risk, nonmetastatic GTN cures 40% of patients without significant morbidity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov/, NCT00521118.
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Legrado , Enfermedad Trofoblástica Gestacional , Reoperación , Adolescente , Adulto , Gonadotropina Coriónica/análisis , Legrado/efectos adversos , Legrado/métodos , Legrado/estadística & datos numéricos , Femenino , Enfermedad Trofoblástica Gestacional/sangre , Enfermedad Trofoblástica Gestacional/diagnóstico , Enfermedad Trofoblástica Gestacional/epidemiología , Enfermedad Trofoblástica Gestacional/patología , Humanos , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Embarazo , Pronóstico , Estudios Prospectivos , Reoperación/métodos , Reoperación/estadística & datos numéricos , Medición de Riesgo , Factores de Riesgo , Ultrasonografía/métodos , Estados Unidos/epidemiologíaRESUMEN
PURPOSE: To review and report the long-term treatment-induced adverse events (AEs) and outcomes of concomitant chemoradiotherapy boosted by low-dose-rate (LDR) conventional brachytherapy (BT) planning in patients with locoregionally advanced cervical cancer. PATIENTS AND METHODS: After obtaining institutional review board approval, we reviewed the records of patients with stage IB1 to IVA, intact cervical cancer who were treated at our institution between 1983 and 2009. Eligible patients underwent definitive radiotherapy with external-beam radiation concomitant with cisplatin-based chemotherapy and boosted by LDR BT. Patient, tumor, and treatment characteristics; treatment-induced AEs, namely, gastrointestinal and genitourinary toxicities, as well as treatment outcomes; locoregional control (LRC), distant control (DC), progression-free survival (PFS), and overall survival (OS) were reviewed and reported. RESULTS: The study included 129 eligible cervical cancer patients; the median age was 46 years (mean, 47 ± 11 y; range, 28 to 81 y), consisting of stages I, II, III, and IV (29.5%, 48.1%, 17.8%, and 4.6%, respectively). The median follow-up was 37 months (mean, 58 ± 59 mo; range, 3 to 275 mo). The 3-year OS, PFS, LRC, and DC were 75.9%, 71.6%, 84.7%, and 80.2%, respectively. The 5-year OS, PFS, LRC, and DC were 70.7%, 68.7%, 84.7%, and 78.3%, respectively. The 10-year OS, PFS, LRC, and DC were 68.7%, 62.3%, 82.5%, and 73.2%, respectively. Gastrointestinal and genitourinary grade 3 and 4 acute AEs were reported in 3.9% and 0%, and chronic grade 3 and 4 AEs were reported in 20.9% and 12.4% of all patients, respectively. CONCLUSIONS: Definitive chemoradiotherapy followed by conventional LDR BT boost is effective, feasible, and tolerable treatment modality for cervical cancer. A comparison with MRI image-guided BT shows comparable treatment outcomes with superior OS in favor of LDR BT but inferior LC with a relatively worse toxicity profile.
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Braquiterapia/efectos adversos , Carcinoma/radioterapia , Neoplasias del Cuello Uterino/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Braquiterapia/métodos , Carcinoma/tratamiento farmacológico , Carcinoma/mortalidad , Quimioradioterapia/métodos , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/mortalidadRESUMEN
OBJECTIVE: To determine clinical factors that contributed to death from gestational trophoblastic neoplasia (GTN) at the Brewer Trophoblastic Disease Center from 1979-2012 compared to 1962-1978. METHODS: Nineteen women who died of GTN from 1979-2012 were retrospectively identified and compared to 45 women previously reported on who died of GTN from 1962-1978. Clinical factors analyzed included demographics, pretreatment human chorionic gonadotropin (hCG) level, duration of disease, antecedent pregnancy, number and sites of metastases, FIGO stage and score, treatment, and cause of death. RESULTS: Death from GTN occurred in 19 (4%) of 483 patients treated from 1979-2012 compared to 45 (11%) of 396 patients treated from 1962-1978 (P<0.001). Pretreatment hCG level >100,000 mIU/mL, time from pregnancy event to treatment >4 months, nonmolar antecedent pregnancy and use of surgery to control metastatic disease were similar between the two treatment eras. Patients in the recent series were more likely to have presented with FIGO IV disease or brain metastasis, been initially treated with multiagent chemotherapy, and received treatment before referral to our center compared to the earlier series. The most common causes of death from 1979-2012 and 1962-1978 were hemorrhage from one or more metastatic sites (11% vs. 42%), respiratory failure (37% vs. 31%), and multiorgan failure due to widespread chemoresistant disease (42% vs. 8%), respectively. CONCLUSIONS: Our overall survival rate in patients with gestational trophoblastic neoplasia improved from 89% in 1962-1978 to 96% in 1979-2012. More patients treated between 1979-2012 died from widespread chemoresistant disease rather than hemorrhagic complications.
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Enfermedad Trofoblástica Gestacional/mortalidad , Enfermedad Trofoblástica Gestacional/terapia , Adolescente , Adulto , Chicago/epidemiología , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Supportive oncology practice can be enhanced by the integration of a brief and validated electronic patient-reported outcome assessment into the electronic health record (EHR) and clinical workflow. METHODS: Six hundred thirty-six women receiving gynecologic oncology outpatient care received instructions to complete clinical assessments through Epic MyChart, an EHR patient communication portal. Patient Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CATs) were administered to assess fatigue, pain interference, physical function, depression, and anxiety. Checklists identified psychosocial concerns, informational and nutritional needs, and risk factors for inadequate nutrition. Assessment results, including PROMIS T scores with documented severity thresholds, were immediately populated in the EHR. Clinicians were notified of clinically elevated symptoms through EHR messages. EHR integration was designed to provide automated triage to social work providers for psychosocial concerns, to health educators for information, and to dietitians for nutrition-related concerns. RESULTS: Four thousand forty-two MyChart messages sent, and 3203 (79%) were reviewed by patients. The assessment was started by 1493 patients (37%), and once they started, 93% (1386 patients) completed the assessment. According to first assessments only, 49.8% of the patients who reviewed the MyChart message completed the assessment. Mean PROMIS CAT T scores indicated a lower level of physical function and elevated anxiety in comparison with the general population. Fatigue, pain, and depression scores were comparable to those of the general population. Impaired physical functioning was the most common basis for clinical alerts and occurred in 4% of the patients. CONCLUSIONS: PROMIS CATs were used to measure common cancer symptoms in routine oncology outpatient care. Immediate EHR integration facilitated the use of symptom reporting as the basis for referral to psychosocial and supportive care.
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Atención Ambulatoria/métodos , Registros Electrónicos de Salud , Neoplasias de los Genitales Femeninos/fisiopatología , Neoplasias de los Genitales Femeninos/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Cuidados Paliativos/métodos , Autoinforme , Encuestas y Cuestionarios , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVES: The objective of this study was to compare outcomes for patients with cervical cancer treated with radiation concurrently with cisplatin, cisplatin/5-fluorouracil (5-FU), or without chemotherapy. MATERIALS AND METHODS: We reviewed the records of eligible patients with locoregionally confined, stage IB1 through IVA, intact cervical cancer who were treated at Northwestern Memorial Hospital. All patients underwent definitive radiotherapy with combined external beam radiation-the majority with extended-field (62%)-and received low-dose rate brachytherapy. RESULTS: A total of 236 patients were included: 99 had no concurrent chemotherapy, 95 were treated with concurrent cisplatin, and 42 were treated with cisplatin/5-FU. For all patients treated with or without chemotherapy, overall survival at 5 and 10 years was 64% and 59%, respectively. Patients treated with chemotherapy had a superior recurrence-free survival rate of 69% at 5 years versus 49% in patients who did not receive chemotherapy (P=0.09). Twenty-six percent of patients treated with cisplatin alone, 31% of patients treated with cisplatin/5-FU, and 45% of patients who did not receive chemotherapy experienced a disease recurrence. Adenosquamous histology conferred a higher rate of recurrence as compared with adenocarcinoma and squamous cell histologies (54% vs. 34%, respectively; P=0.05). CONCLUSIONS: Cisplatin-based concurrent chemoradiotherapy showed a trend toward improved recurrence-free survival survival in the definitive treatment of nonmetastatic cervical cancer. The addition of 5-FU to cisplatin did not appear to significantly impact survival or recurrence-free survival. Adenosquamous histology was associated with a higher risk of recurrence as compared with other histologic subtypes.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/radioterapia , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Braquiterapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/administración & dosificación , Humanos , Persona de Mediana Edad , Resultado del Tratamiento , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
OBJECTIVE: The purpose of this study was to assess knowledge of the human papillomavirus (HPV), cervical cancer, and HPV vaccination in African American women (AAW). STUDY DESIGN: This study was a quantitative cross-sectional survey of English-speaking, AAW, 18-70 years old who were recruited from a community fair in Chicago, IL. Surveys were distributed to a convenience sample to assess knowledge of HPV, cervical cancer, and the HPV vaccine. Cumulative knowledge scores were calculated for each participant, and analysis was performed to identify factors that were associated with adequate knowledge scores. RESULTS: Three hundred twenty-two surveys were distributed; 242 surveys were collected, and 215 surveys met inclusion criteria. Mean knowledge score was 12.3 ± 4.2 (mean ± SD) of a maximum score of 28 (range, 3-23); 73% of participants scored <65% on the knowledge portion of the survey. Education level (P = .007), household income (P = .010), and having a child who had been offered the HPV vaccine (P = .041) were associated with adequate (≥65% accuracy) knowledge scores. CONCLUSION: Knowledge of HPV, cervical cancer, and HPV vaccination was low in this urban African American adult female population. Targeted educational health programs are needed to increase awareness among these women who have the highest rate of cervical cancer mortality in the United States. Such patient educational programs must be developed by physicians and should address the cultural and literacy needs of this particular group of women. In addition, AAW exert influence on the health of their communities and are integral in health-related decision-making; thus, educating them through their health care providers will have far ranging impact.
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Negro o Afroamericano , Conocimientos, Actitudes y Práctica en Salud , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: This study examined the content validity of the NCCN-FACT Ovarian Symptom Index-18 (NFOSI-18), an advanced ovarian cancer symptom index comprised of symptoms perceived as most important by clinical experts and women with advanced ovarian cancer. METHODS: Eighteen women with advanced ovarian cancer completed the NFOSI-18 and participated in cognitive interviews to assess: (a) the understandability of the NFOSI-18; and (b) the things patients have in mind when responding to the item, "I am bothered by side effects of treatment;" and (c) the interpretation patients place on items relating to fatigue and lack of energy. Interviews were recorded and transcribed for qualitative analysis. RESULTS: All but 2 (89%) participants indicated that each item was clear and understandable and the same proportion (89%) stated they were "very confident" or "confident" about providing accurate answers to all but one item. When responding to the item, "I am bothered by side effects of treatment," fatigue, nausea, and neuropathy constituted the most frequently mentioned concerns. Among the participants who were asked, eight participants responded that "fatigue" and "lack of energy" were the same concept and nine responded they were different. Participants associated "fatigue" with tiredness and associated "lack of energy" with the inability to perform daily tasks and activities. CONCLUSIONS: The findings support the content validity of the NFOSI-18. Item revisions, deletions or additions do not appear warranted. Future research can address the reliability and validity of the NFOSI-18 in clinical research.
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Neoplasias Ováricas/diagnóstico , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/clasificación , Calidad de Vida , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Resistance to progestin treatment is a major hurdle in the treatment of advanced and reoccurring endometrial cancer. Fenretinide is a synthetic retinoid that has been evaluated in clinical trials as a cancer therapeutic and chemo-preventive agent. Fenretinide has been established to be cytotoxic to many kinds of cancer cells. In the present study, we demonstrate that fenretinide decreased cell viability and induced apoptosis in Ishikawa cells, which are an endometrial cancer cell line, in dose dependent manner in-vitro. This effect was found to be independent of retinoic acid nuclear receptor signaling pathway. Further, we have shown that this induction of apoptosis by fenretinide may be caused by increased retinol uptake via STRA6. Silencing of STRA6 was shown to decrease apoptosis which was inhibited by knockdown of STRA6 expression in Ishikawa cells. Results of an in-vivo study demonstrated that intraperitoneal injections of fenretinide in endometrial cancer tumors (created using Ishikawa cells) in mice inhibited tumor growth effectively. Immunohistochemistry of mice tumors showed a decrease in Ki67 expression and an increase in cleaved caspase-3 staining after fenretinide treatment when compared to vehicle treated mice. Collectively, our results are the first to establish the efficacy of fenretinide as an antitumor agent for endometrial cancer both in-vitro and in-vivo, providing a valuable rationale for initiating more preclinical studies and clinical trials using fenretinide for the treatment of endometrial cancer.
Asunto(s)
Neoplasias Endometriales/tratamiento farmacológico , Fenretinida/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Progresión de la Enfermedad , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Fenretinida/farmacología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Acetato de Megestrol/farmacología , Proteínas de la Membrana/metabolismo , Ratones Desnudos , Vitamina A/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE(S): The aims of this study were to analyze patterns of recurrence in patients with ovarian clear cell adenocarcinoma (CCA) and to evaluate the role of pelvic radiotherapy (RT). METHODS AND MATERIALS: All patients with ovarian CCA treated at a single institution between 1989 and 2012 were identified, and their medical records were reviewed. Eligibility criteria included histologic diagnosis of pure CCA of the ovary, surgical staging for International Federation of Gynecology and Obstetrics stage I-to-IIIC disease, and adjuvant or neoadjuvant chemotherapy. Selected end points were 3-, 5-, and 8-year cumulative incidence of pelvic recurrence (CIPR). RESULTS: Fifty-six patients met eligibility criteria. Most received intravenous carboplatin and paclitaxel for a median of 6 cycles. Six patients (10.7%) received pelvic RT, and 50 (89.3%) did not. Pelvic RT patients had stage I-to-IIC disease. Median follow-up was 39 months (range, 1-69 months). For the group as a whole, 14 patients (25%) had initial disease recurrence involving the pelvis, whereas 6 (10.7%) had first recurrence outside the pelvis. Three-, 5- and 8-year CIPR were 28.2%, 38.5%, and 43.2%, respectively. There was no significant difference in 3-, 5-, or 8-year CIPR between the group of patients receiving RT (20%, 20%, and 20%) and a group of patients with stages I to IIC who did not receive RT (9.9%, 22.4%, and 30.2%), P = 0.22. During RT, patients developed mild grade 1-to-2 side effects. After RT, 1 patient developed lower extremity lymphedema with recurrent cellulitis. One patient who developed small bowel obstruction before RT developed small bowel radiation enteritis and obstruction after RT, ultimately requiring surgical intervention. CONCLUSIONS: These findings suggest that ovarian CCA exhibits a propensity for pelvic recurrence after surgery and chemotherapy. RT, a local treatment that can effectively sterilize microscopic tumor cells, may benefit patients with this disease. Prospective studies with sufficient statistical power are warranted to further evaluate the role of RT.
Asunto(s)
Adenocarcinoma de Células Claras/complicaciones , Neoplasias Endometriales/complicaciones , Recurrencia Local de Neoplasia/prevención & control , Neoplasias Glandulares y Epiteliales/complicaciones , Neoplasias Ováricas/complicaciones , Neoplasias Pélvicas/radioterapia , Adenocarcinoma de Células Claras/patología , Adenocarcinoma de Células Claras/terapia , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Epitelial de Ovario , Chicago/epidemiología , Terapia Combinada , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Persona de Mediana Edad , Clasificación del Tumor , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/terapia , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Neoplasias Pélvicas/etiología , Neoplasias Pélvicas/patología , Pronóstico , Estudios RetrospectivosRESUMEN
BACKGROUND: Molecular biomarkers, a cornerstone of precision oncology, are critical in breast, gastroesophageal, and non-small cell lung cancer management (BC, GEC, NSCLC). Testing practices are intensely debated, impacting diagnostic quality and affecting pathologists, oncologists and patients. However, little is known about testing approaches used in practice. Our study described biomarker practices in BC, GEC, and NSCLC at the leading US cancer centers. METHODS: We conducted a survey of the National Cancer Institute (NCI) designated centers on BC, GEC, and NSCLC biomarker testing. We used simple frequencies to describe practices, two-sided Fisher's exact test and two-sided McNemar's test for cross-cancer comparison. All statistical tests were two-sided. RESULTS: For BC human epidermal growth factor receptor 2 (HER2), 39% of centers combine guidelines by using in situ hybridization (ISH) and immunohistochemistry (IHC) concurrently, and 21% reflex-test beyond guideline-recommended IHC2+. For GEC HER2, 44% use ISH and IHC concurrently, and 28% reflex-test beyond IHC2+. In NSCLC, the use of IHC is limited to 4% for epidermal growth factor receptor (EGFR) and 7% for anaplastic lymphoma kinase (ALK). 43.5% test NSCLC biomarkers on oncologist order; 34.5% run all biomarkers upfront, and 22% use a sequential protocol. NSCLC external testing is statistically significantly higher than BC (P < .0001) and GEC (P < .0001). NSCLC internally developed tests are statistically significantly more common than BC (P < .0001) and GEC (P < .0001). CONCLUSIONS: At the NCI cancer centers, biomarker testing practices vary, but exceeding guidelines is a common practice for established biomarkers and emerging practice for newer biomarkers. Use of internally developed tests declines as biomarkers mature. Implementation of multibiomarker protocols is lagging. Our study represents a step toward developing a biomarker testing practice landscape.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias de la Mama/química , Neoplasias Esofágicas/química , Neoplasias Pulmonares/química , Pautas de la Práctica en Medicina/estadística & datos numéricos , Neoplasias Gástricas/química , Adulto , Quinasa de Linfoma Anaplásico , Instituciones Oncológicas , Carcinoma de Pulmón de Células no Pequeñas/química , Factores de Confusión Epidemiológicos , Estudios Transversales , Receptores ErbB/análisis , Femenino , Humanos , Inmunohistoquímica , Hibridación in Situ , Internet , Masculino , Persona de Mediana Edad , National Cancer Institute (U.S.) , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina/tendencias , Proteínas Proto-Oncogénicas/análisis , Proteínas Proto-Oncogénicas p21(ras) , Proteínas Tirosina Quinasas Receptoras/análisis , Receptor ErbB-2/análisis , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Autoinforme , Encuestas y Cuestionarios , Estados Unidos , Proteínas ras/análisisRESUMEN
OBJECTIVE: To identify patient characteristics, determine prognostic factors, and evaluate outcomes for women with hepatic metastases in gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Seventeen GTN patients with hepatic metastases were treated at our institution between 1962 and 2010. Demographic data, disease characteristics, and survival were all analyzed retrospectively. Fisher's exact test was used to determine significance. RESULTS: The median age was 29 years (range, 16-48), and the antecedent pregnancy was nonmolar in 12 patients (75%) and a hydatidiform mole in 4 patients (25%). Fifteen patients (88%) had metastatic disease outside the liver, including lung (13), brain (5), and other intraabdominal organs (8). Median FIGO score was 14 (range, 12-19). Chemotherapy consisted of single-agent methotrexate or actinomycin D in 2 patients; methotrexate, actinomycin D, cyclophosphamide (MAC) in 4 patients; and etoposide, methotrexate, actinomycin D, cyclophosphamide and vincristine (EMACO) in 11 patients. Complete response rate to chemotherapy was 82% for EMA-CO versus 17% for other types of chemotherapy (p = 0.035). Overall survival was 41% (7/17). CONCLUSION: Survival of patients with GTN and hepatic metastases increased from 17% (1/6) to 55% (6/11) after 1986 when EMA-CO chemotherapy was introduced. Survival was significantly decreased for patients with concomitant intraabdominal or brain metastases (11% vs. 75%, p = 0.015).
Asunto(s)
Enfermedad Trofoblástica Gestacional/patología , Neoplasias Hepáticas/secundario , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Coriocarcinoma/secundario , Ciclofosfamida/uso terapéutico , Dactinomicina/uso terapéutico , Etopósido/uso terapéutico , Femenino , Humanos , Mola Hidatiforme/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Metotrexato/uso terapéutico , Persona de Mediana Edad , Metástasis de la Neoplasia/patología , Embarazo , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Neoplasias Uterinas/patología , Vincristina/uso terapéutico , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to define the incidence and prognostic significance of venous thromboembolism (VTE) in patients with advanced, epithelial ovarian cancer undergoing frontline adjuvant chemotherapy after an extended period (28 days) of postoperative prophylaxis. METHODS: A retrospective analysis of patients with advanced, epithelial ovarian cancer who underwent surgery and chemotherapy at a single institution from January 2008 through December 2011 was performed. Exclusion criteria were history of VTE, VTE during the postoperative period, clear cell histology, use of anticoagulation for a different indication, and lack of compliance with 28 days of postoperative prophylaxis with a low-molecular-weight heparin. Baseline patient demographics and oncologic outcomes were analyzed. Clinically symptomatic VTE was identified and confirmed with imaging studies. Otherwise, VTE was identified on imaging studies done to assess disease status at the conclusion of adjuvant chemotherapy. RESULTS: One hundred twenty-eight patients met criteria for inclusion. Sixteen patients had a reported VTE during the time they were on frontline chemotherapy (12.5%). Nine patients (7%) had a pulmonary embolus, and 8 (6.3%) had a deep vein thrombus. The mean BMI in the group that developed VTE was 28, and in the group without VTE, it was 26.5 (P = 0.23). Three (23%) of the 16 patients who developed VTE had undergone a suboptimal cytoreduction compared with 12 (11%) of the 112 in the group with no VTE (P = 0.4). Six (37%) of the 16 patients who developed VTE during chemotherapy underwent a bowel resection and/or splenectomy during their cytoreductive surgery compared with 18 (16%) of the 112 patients who did not develop VTE (P = 0.079). Eight of the patients in the VTE group had indwelling venous catheters during chemotherapy (50%) compared with 39 (35%) in the group with no VTE (P = 0.27). In the group that developed VTE, there was a trend toward increased preoperative CA-125, higher rates of bowel resection and/or splenectomy during surgery, decreased use of aspirin, and inferior survival. On multivariate analysis, patients who developed VTE had significantly longer postoperative hospital stays (7 vs 5 days [P = 0.009]) and lower rates of complete response (P = 0.01). CONCLUSIONS: A 12.5% risk for VTE merits consideration of prophylaxis during chemotherapy in this cohort. A randomized, controlled trial is needed to clarify whether the benefits of long-term prophylaxis outweigh the risks and costs of such therapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Papilar/tratamiento farmacológico , Cistadenocarcinoma Seroso/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Tromboembolia Venosa/inducido químicamente , Carcinoma Papilar/patología , Quimioterapia Adyuvante , Cistadenocarcinoma Seroso/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tromboembolia Venosa/diagnósticoRESUMEN
The participation of racial and ethnic minorities and underserved populations in clinical trials is a critical link between scientific innovation and improvements in health care delivery and health outcomes. However, these population groups continue to be underrepresented in research. We describe the development of the Cancer Disparities Research Network (CDRN) to improve minority and underserved populations' participation in biobanking research. Between February and October 2011, we conducted a regional assessment to identify challenges and opportunities for cancer trials and biobanking research across the CDRN. Representatives from ten CDRN biorepository facilities completed an online survey assessing their facilities' minority biospecimen collection, biobanking practices, and education/outreach initiatives. Representatives of eight facilities also participated in stakeholder interviews. The majority (70%) of facilities reported that specimens were available for research, although only one tenth of these specimens were from non-White patients. Most facilities collected a patient's age, gender, race, medical history, and ethnicity with samples; however, less than half also collected family health history, education level, household income, or primary language spoken. In addition, few institutions collected Asian or Hispanic subgroup information. Only a few reported biospecimen collection outreach programs specifically targeting minority and underserved populations. Biospecimen directors and administrators indicated that funding, biospecimen sharing procedures, and standardization barriers limited their facilities from collaborating in biospecimen collection programs, despite their great interest. These findings suggest that the CDRN can provide opportunities for collaboration, resource sharing, and fostering of research ideas to address cancer disparities in biospecimen research.