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
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
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
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
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.
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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.
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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.
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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).
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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: We reviewed data on treatment of stage IB1 cervical cancer at our institution to compare recurrence, complications, and survival of women treated primarily by radical hysterectomy versus radiation. METHODS: Records for women treated for stage IB1 cervical cancer between January 1, 1990 and June 1, 2010 were retrospectively reviewed. Recurrence, survival outcomes, and complications were examined and compared. Demographic, clinical, and histopathologic factors were also analyzed. RESULTS: Of 198 patients with stage IB1 cervix cancer, 169 (85%) underwent radical hysterectomy, including 37 (20%) who received postoperative radiation, and 29 (15%) were treated primarily with radiotherapy±chemotherapy. Progression-free survival, overall survival, and disease-specific survival were all longer in the surgery group (89%, 95%, and 96%) versus the radiation group (70%, 70%, and 78%), respectively (P<0.001). Patients in the radiation group were older, had larger tumors, and were more likely to have medical comorbidities than patients in the surgery group. Within the surgical cohort, lymphvascular space invasion, outer third cervical stromal invasion, positive surgical margins, and lymph node metastasis were all predictive of recurrence (P<0.002), whereas histopathology, smoking, diabetes, and immunosuppression were not. Grade 3 or 4 complication rates were higher among the 29 patients who had primary radiotherapy (20.7%) and the 37 patients who had surgery followed by radiotherapy (21.6%) compared with the 132 patients who had surgery only (9.1%) (P=0.047). CONCLUSIONS: Primary treatment of stage IB1 cervix cancer with radical hysterectomy±adjuvant radiation resulted in a significantly lower rate of recurrence and an improved survival with fewer complications compared with radiotherapy with or without chemotherapy.
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Histerectomía , Neoplasias del Cuello Uterino/radioterapia , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Histerectomía/efectos adversos , Histerectomía/métodos , Illinois/epidemiología , Estimación de Kaplan-Meier , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Registros Médicos , Persona de Mediana Edad , Invasividad Neoplásica , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/epidemiología , Estadificación de Neoplasias , Selección de Paciente , Radioterapia Adyuvante , Estudios Retrospectivos , Sesgo de Selección , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/patologíaRESUMEN
BACKGROUND: Basic science studies suggest that perioperative immune impairment may augment the risk of cancer recurrence after otherwise potentially curative surgery. Despite its immunosuppressant properties, dexamethasone is commonly given to oncologic patients in an effort to reduce postoperative nausea and vomiting. We therefore tested the hypothesis that perioperative dexamethasone administration increases the risk of ovarian cancer recurrence. METHODS: Women who had primary ovarian cytoreductive surgery between January 1997 and October 2007 were identified using a database maintained by the division of Gynecologic Oncology at Northwestern University. Tumor recurrence in women given perioperative systemic dexamethasone (4-10 mg) was compared with those who did not receive dexamethasone. The primary outcome was the propensity-matched time to cancer recurrence. Recurrence was defined by a carcinoantigen 125 >21 U/mL or computerized tomography evidence of the disease followed by tissue confirmation. Median difference and 95% confidence interval between the propensity-matched groups were calculated using a 10,000 sample bootstrap. RESULTS: Among 260 women having primary cytoreductive surgery for ovarian cancer that met our inclusion criteria, 102 subjects were given perioperative systemic dexamethasone. Cancer recurrence was observed in 178 subjects, and the overall unadjusted median (IQR) time to recurrence was 18 (7-50) months. Eighty-seven cases and 87 controls were propensity matched to adjust for confounding covariates. After propensity matching the groups for confounding covariates, the median (IQR) time to recurrence in the dexamethasone group was 23 (6-46) compared with 18 (8-53) months in the control group (P = 0.63) with a median (95% confidence interval) difference of time to recurrence between the dexamethasone and the control group of 5 (-8 to 17) months. CONCLUSION: We could not find evidence for an association between perioperative systemic dexamethasone administration and ovarian cancer recurrence after primary cytoreductive surgery. Our results do not support avoiding low-dose perioperative dexamethasone for prevention of postoperative nausea, vomiting, and pain in ovarian cancer patients.
Asunto(s)
Antieméticos/efectos adversos , Dexametasona/efectos adversos , Neoplasias Ováricas/etiología , Anciano , Antineoplásicos/uso terapéutico , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Cuidados Intraoperatorios , Estimación de Kaplan-Meier , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neoplasias Ováricas/cirugía , Cuidados Posoperatorios , Puntaje de Propensión , Factores Socioeconómicos , Resultado del TratamientoRESUMEN
OBJECTIVE: To quantify the number of follicles in patients with ovarian pathologies, benign and malignant, in pregnant and nonpregnant states and to determine how the presence of ovarian masses and BRCA status affects follicular counts. MATERIALS AND METHODS: Slides from 134 reproductive-aged women undergoing oophorectomy were examined using light microscopy by 3 independent counters blinded to the diagnosis. In all, 20 patients had cancer, 69 had benign conditions, and 35 patients were BRCA+ or had a strong family history of breast and/or ovarian cancer. In all, 10 women were either pregnant or immediately postpartum. RESULTS: Patients undergoing risk-reducing surgery had significantly decreased follicle count compared to physiologic control. Patients with cancer had significantly decreased counts compared to all other groups. There were no differences within the benign cohort. CONCLUSIONS: When compared to benign masses, the cortex surrounding an ovarian malignancy has decreased follicle density. The stretch impact may minimize any impact on total follicle numbers. Furthermore, there may be a proliferation of ovarian stroma, with the same number of follicles spread over a larger surface area. This information is important when counseling women with ovarian masses regarding the use of ovarian tissue cryopreservation.
Asunto(s)
Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Ovario/metabolismo , Ovario/patología , Adolescente , Adulto , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Embarazo , Método Simple Ciego , Adulto JovenRESUMEN
AIMS: Comparing effectiveness of diagnostic tests is one of the highest priorities for comparative effectiveness research (CER) set by the Institute of Medicine. Our study aims to identify what information providers, payers and patients need from CER on diagnostics, and what challenges they encounter implementing comparative information on diagnostic alternatives in practice and policy. MATERIALS & METHODS: Using qualitative research methods and the example of two alternative protocols for HER2 testing in breast cancer, we conducted interviews with 45 stakeholders: providers (n = 25) from four academic and eight nonacademic institutions, executives (n = 13) from five major US private payers and representatives (n = 7) from two breast cancer patient advocacies. RESULTS: The need for additional scientific evidence to determine the preferred HER2 protocol was more common for advocates than payers (100 vs 54%; p = 0.0515) and significantly more common for advocates than providers (100 vs 40%; p = 0.0077). The availability of information allowing assessment of the implementation impact from alternative diagnostic protocols on provider institutions may mitigate the need for additional scientific evidence for some providers and payers (24 and 46%, respectively). The cost-effectiveness of alternative protocols from the societal perspective is important to payers and advocates (69 and 71%, respectively) but not to providers (0%; p = 0.0001 and p = 0.0001). The lack of reporting laboratory practices is a more common implementation challenge for payers and advocates (77 and 86%, respectively) than for providers (32%). The absence of any mechanism for patient involvement was recognized as a challenge by payers and advocates (69 and 100%, respectively) but not by providers (0%; p = 0.0001 and p = 0.0001). CONCLUSION: Comparative implementation research is needed to inform the stakeholders considering diagnostic alternatives. Transparency of laboratory practices is an important factor in enabling implementation of CER on diagnostics in practice and policy. The incongruent views of providers versus patient advocates and payers on involving patients in diagnostic decisions is a concerning challenge to utilizing the results of CER.
Asunto(s)
Neoplasias de la Mama/diagnóstico , Investigación sobre la Eficacia Comparativa , Receptor ErbB-2/metabolismo , Actitud del Personal de Salud , Neoplasias de la Mama/economía , Análisis Costo-Beneficio , Toma de Decisiones , Detección Precoz del Cáncer , Femenino , Adhesión a Directriz , Humanos , Illinois , Difusión de la Información , Seguro de Salud , Evaluación de Necesidades , Defensa del Paciente , Guías de Práctica Clínica como Asunto , Sector Privado , Práctica Profesional , Investigación CualitativaRESUMEN
These NCCN Guidelines Insights focus on the major updates to the 2013 NCCN Guidelines for Ovarian Cancer. Four updates were selected based on recent important updates in the guidelines and on debate among panel members about recent clinical trials. The topics include 1) intraperitoneal chemotherapy, 2) CA-125 monitoring for ovarian cancer recurrence, 3) surveillance recommendations for less common ovarian histopathologies, and 4) recent changes in therapy for recurrent epithelial ovarian cancer. These NCCN Guidelines Insights also discuss why some recommendations were not made.
Asunto(s)
Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/terapia , Femenino , Humanos , RecurrenciaRESUMEN
OBJECTIVE: Use of in vitro chemoresponse assays for informing effective treatment selection is a compelling clinical question and a topic of debate among oncologists. A prospective study was conducted evaluating the use of a chemoresponse assay in recurrent ovarian cancer patients. METHODS: Women with persistent or recurrent ovarian cancer were enrolled under an IRB-approved protocol, and fresh tissue samples were collected for chemoresponse testing. Patients were treated with one of 15 protocol-designated treatments empirically selected by the oncologist, blinded to the assay results. Each treatment was classified by the assay as: sensitive (S), intermediate (I), or resistant (R). Patients were prospectively monitored for progression-free survival (PFS) and overall survival (OS). Associations of assay response for the physician-selected treatment with PFS and OS were analyzed. RESULTS: A total of 262 evaluable patients were enrolled. Patients treated with an assay-sensitive regimen demonstrated significantly improved PFS and OS while there was no difference in clinical outcomes between I and R groups. Median PFS was 8.8 months for S vs. 5.9 months for I+R (hazard ratio [HR]=0.67, p=0.009). The association with assay response was consistent in both platinum-sensitive and platinum-resistant tumors (HR: 0.71 vs. 0.66) and was independent of other covariates in multivariate analysis (HR=0.66, p=0.020). A statistically significant14-month improvement in mean OS (37.5 months for S vs. 23.9 months for I+R, HR=0.61, p=0.010) was demonstrated. CONCLUSIONS: This prospective study demonstrated improved PFS and OS for patients with either platinum-sensitive or platinum-resistant recurrent ovarian cancer treated with assay-sensitive agents.
Asunto(s)
Neoplasias Glandulares y Epiteliales/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Anciano , Carcinoma Epitelial de Ovario , Supervivencia sin Enfermedad , Método Doble Ciego , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias de las Trompas Uterinas/tratamiento farmacológico , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Peritoneales/tratamiento farmacológico , Estudios Prospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the efficacy, progression-free survival (PFS) and overall survival (OS) for the combination of intravenous bevacizumab and oral cyclophosphamide in heavily pretreated patients with recurrent ovarian carcinoma. METHODS: A retrospective review was performed for all patients with recurrent ovarian carcinoma treated with intravenous bevacizumab 10 mg/kg every 14 days and oral cyclophosphamide 50 mg daily between January 2006 and December 2010. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors criteria and/or CA-125 levels. RESULTS: Sixty-six eligible patients were identified. Median age was 53 years. Fifty-five patients (83%) had undergone optimal cytoreduction. All patients were primarily or secondarily platinum resistant at the time of administration of bevacizumab and cyclophosphamide. The median number of prior chemotherapy treatments was 6.5 (range, 3 to 16). Eight patients (12.1%) had side effects which required discontinuation of bevacizumab and cyclophosphamide. There was one bowel perforation (1.5%). Overall response rate was 42.4%, including, complete response in 7 patients (10.6%), and partial response in 21 patients (31.8%), while 15 patients (22.7%) had stable disease and 23 patients (34.8%) had disease progression. Median PFS for responders was 5 months (range, 2 to 14 months). Median OS from initiation of bevacizumab and cyclophosphamide was 20 months (range, 2 to 56 months) for responders and 9 months (range, 2 to 51 months) for non-responders (p=0.004). CONCLUSION: Bevacizumab and cyclophosphamide is an effective, well-tolerated chemotherapy regimen in heavily pretreated patients with recurrent ovarian carcinoma. This combination significantly improved PFS and OS in responders. Response rates were similar and favorable to the rates reported for similar patients receiving other commonly used second-line chemotherapeutic agents.