RESUMO
We have previously shown that vaccination with tumor-pulsed dendritic cells amplifies neoantigen recognition in ovarian cancer. Here, in a phase 1 clinical study ( NCT01312376 /UPCC26810) including 19 patients, we show that such responses are further reinvigorated by subsequent adoptive transfer of vaccine-primed, ex vivo-expanded autologous peripheral blood T cells. The treatment is safe, and epitope spreading with novel neopeptide reactivities was observed after cell infusion in patients who experienced clinical benefit, suggesting reinvigoration of tumor-sculpting immunity.
Assuntos
Neoplasias Ovarianas , Vacinas , Humanos , Feminino , Neoplasias Ovarianas/terapia , Transferência Adotiva , Vacinação , Linfócitos TRESUMO
OBJECTIVES: Patients with gynecologic malignancies may have varied responses to COVID-19 infection. We aimed to describe clinical courses, treatment changes, and short-term clinical outcomes for gynecologic oncology patients with concurrent COVID-19 in the United States. METHODS: The Society of Gynecologic Oncology COVID-19 and Gynecologic Cancer Registry was created to capture clinical courses of gynecologic oncology patients with COVID-19. Logistic regression models were employed to evaluate factors for an association with hospitalization and death, respectively, within 30 days of COVID-19 diagnosis. RESULTS: Data were available for 348 patients across 7 institutions. At COVID-19 diagnosis, 125 patients (36%) had active malignancy. Delay (n = 88) or discontinuation (n = 10) of treatment due to COVID-19 infection occurred in 28% with those on chemotherapy (53/88) or recently receiving surgery (32/88) most frequently delayed. In addition to age, performance status, diabetes, and specific COVID symptoms, both non-White race (adjusted odds ratio (aOR) = 3.93, 95% CI 2.06-7.50) and active malignancy (aOR = 2.34, 95% CI 1.30-4.20) were associated with an increased odds of hospitalization. Eight percent of hospitalized patients (8/101) died of COVID-19 complications and 5% (17/348) of the entire cohort died within 30 days after diagnosis. CONCLUSIONS: Gynecologic oncology patients diagnosed with COVID-19 are at risk for hospitalization, delay of anti-cancer treatments, and death. One in 20 gynecologic oncology patients with COVID-19 died within 30 days after diagnosis. Racial disparities exist in patient hospitalizations for COVID-19, a surrogate of disease severity. Additional studies are needed to determine long-term outcomes and the impact of race.
Assuntos
COVID-19 , Neoplasias dos Genitais Femininos , Humanos , Feminino , Estados Unidos/epidemiologia , COVID-19/terapia , Neoplasias dos Genitais Femininos/terapia , Teste para COVID-19 , Hospitalização , Sistema de Registros , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the utilization and outcomes of ovarian preservation for premenopausal patients with International Federation of Gynecology and Obstetrics (FIGO) stage I grade 2 and 3 endometrioid endometrial carcinoma undergoing hysterectomy. METHODS: The National Cancer Database was accessed; patients aged ≤45 years diagnosed between January 2004 and December 2015 with FIGO stage I grade 2 or 3 endometrioid endometrial carcinoma, who underwent hysterectomy with or without bilateral salpingo-oophorectomy and had at least 1 month of follow-up, were identified. Overall survival was assessed following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected variables. RESULTS: A total of 2941 patients who met the inclusion criteria were identified; 200 (6.8%) patients did not undergo bilateral salpingo-oophorectomy. Rate of ovarian preservation was comparable between patients with grade 2 (n=163, 6.6%) and grade 3 (n=37, 7.7%) tumors (p=0.38). Patients who did not undergo bilateral salpingo-oophorectomy were younger (median 39 vs 41 years, p<0.001) and less likely to undergo surgical lymph node assessment (52% vs 76.2%, p<0.001). There was no difference in overall survival between patients who did and did not undergo bilateral salpingo-oophorectomy (p=0.94); 5 year overall survival rates were 96.6% and 97%, respectively. After controlling for confounders, including tumor grade, ovarian preservation was not associated with worse overall survival (HR 0.92, 95% CI 0.47 to 1.84). CONCLUSIONS: For patients with grade 2 and 3 FIGO stage I endometrioid carcinoma undergoing hysterectomy, ovarian preservation is rarely performed while no clear detrimental effect on overall survival was found.
RESUMO
OBJECTIVE: The administration of adjuvant chemotherapy within 42 days from surgery is one of the proposed quality measures for patients with epithelial ovarian cancer (EOC). The aim of the present study was to evaluate the impact of chemotherapy delay in the survival of patients with stage I EOC. METHODS: The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with FIGO stage I EOC who received multi-agent chemotherapy were identified. Overall survival (OS) was compared between patients who received chemotherapy <6 weeks and 6-12 weeks from surgery with the log-rank test following generation of Kaplan-Meier curves. Cox model was constructed to control for a priori selected confounders. RESULTS: A total of 8549 patients who received adjuvant chemotherapy at a median 35 days from surgery (interquartile range 19) were identified; 67.7% received adjuvant chemotherapy <6 weeks from surgery while 32.3% experienced a delay. Patients who experienced a delay were more likely to have comorbidities (18.4% vs 14.9%, p < 0.001), and be managed in non-academic facilities (57.1% vs 53.2%, p = 0.001). Patients who experienced a delay had worse OS compared to those who did not, p < 0.001; 5-year OS rates 85.7% and 89.7%, respectively. For patients with high-grade serous tumors, those who experienced a delay had a 5-yr OS of 81.9% compared to 88.6% for those who did not, p < 0.001. After controlling for age, race, presence of comorbidities, insurance status, tumor histology and grade, performance of lymphadenectomy and substage, chemotherapy delay was associated with worse survival (HR: 1.25, 95% CI: 1.10, 1.42). CONCLUSIONS: For patients with early stage EOC administration of adjuvant chemotherapy within 6 weeks from surgery was associated with better overall survival, especially for those with stage IC disease.
Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Modelos de Riscos ProporcionaisRESUMO
OBJECTIVE: Investigate the role of lymphadenectomy for patients with apparent stage I uterine sarcoma. METHODS: The National Cancer Database was accessed and patients without a history of another tumor diagnosed between 2004 and 2015 with an apparent early stage leiomyosarcoma, adenosarcoma, low-grade endometrial stromal and high-grade endometrial stromal/undifferentiated sarcoma who underwent hysterectomy with or without lymphadenectomy were identified. Overall survival was assessed after stratification by histology with the log-rank test while Cox models were constructed to control for confounders. RESULTS: A total of 6412 patients with apparent early stage uterine sarcoma who underwent hysterectomy were identified; 2820 (44%) underwent lymphadenectomy. Rate of lymph node metastasis was 3.4% (42/1250) for patients with leiomyosarcoma, 2.3% (19/826) for those with adenosarcoma, 4.5% (21/463) for patients with low-grade endometrial stromal sarcoma and 7.9% (22/280) for those with high-grade endometrial stromal/undifferentiated sarcoma, p < 0.001. After controlling for confounders lymphadenectomy was not associated with better survival for patients with adenosarcoma (HR: 0.92, 95% CI: 0.73, 1.17), or low-grade endometrial stromal sarcoma (HR: 1.17, 95% CI: 0.73, 1.87). Patients with leiomyosarcoma who underwent lymphadenectomy had worse survival (HR: 1.15, 95% CI: 1.03, 1.28). Patients with high-grade endometrial stromal/undifferentiated sarcoma who underwent lymphadenectomy had better survival (HR: 0.66, 95% CI: 0.48, 0.89). CONCLUSIONS: Incidence of lymph node metastasis in apparent early stage uterine sarcoma is rare while the performance of lymphadenectomy was not associated with a clear survival benefit for all histologic subtypes except high-grade endometrial stromal/undifferentiated sarcoma.
Assuntos
Histerectomia/mortalidade , Leiomiossarcoma/cirurgia , Excisão de Linfonodo/mortalidade , Sarcoma do Estroma Endometrial/cirurgia , Neoplasias Uterinas/cirurgia , Feminino , Seguimentos , Humanos , Leiomiossarcoma/patologia , Pessoa de Meia-Idade , Prognóstico , Sarcoma do Estroma Endometrial/patologia , Taxa de Sobrevida , Neoplasias Uterinas/patologiaRESUMO
OBJECTIVE: A retrospective cohort study comparing survival and perioperative outcomes of patients with early vulvar cancer who underwent sentinel lymph node biopsy versus standard lymphadenectomy METHODS: Patients diagnosed between January 2012 and December 2015 with vulvar squamous cell carcinoma of less than 4 cm in size, with invasion of at least 1 mm, who underwent sentinel lymph node biopsy, lymphadenectomy, or both were identified from the National Cancer Database. Overall survival was evaluated following generation of Kaplan-Meier curves and compared with the log-rank test for patients who had at least 1 month of follow-up. A Cox model was constructed to control for confounders. RESULTS: A total of 1583 patients were identified; 304 patients (19.2%) underwent sentinel lymph node biopsy alone. Sentinel lymph node biopsy utilization increased 13.9% between 2012 and 2015. Patients who underwent sentinel node biopsy alone were less likely to have comorbidities compared with those undergoing lymphadenectomy only or sentinel node biopsy with lymphadenectomy (25.3% vs 32.9% vs 31.9%, p=0.042), had smaller tumors (median 1.6 vs 2.0 vs 2.0 cm, p<0.001), and were less likely to have positive lymph nodes (11% vs 19.6% vs 28.1%, p<0.001). There was no difference in 3 year overall survival between the three groups (86.3% vs 82.1% vs 77.9%, p=0.26). After controlling for age, race, insurance, comorbidities, lymph node metastases, and tumor size, sentinel lymph node biopsy alone was not associated with worse overall survival compared with lymphadenectomy (HR 0.86, 95% CI 0.57 to 1.32). The sentinel node only group had shorter inpatient stays compared with lymphadenectomy only (median 1 vs 2 days, p<0.001) and a lower rate of unplanned readmission (1.7% vs 5.0%, p=0.010). CONCLUSIONS: The utilization of sentinel lymph node biopsy is increasing in the management of vulvar cancer and is associated with superior perioperative outcomes without impacting overall survival.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Vulvares/mortalidade , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Estados Unidos/epidemiologia , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgiaRESUMO
PURPOSE: To investigate the epidemiology, clinico-pathological characteristics and outcomes of patients diagnosed with malignant ovarian Sertoli-Leydig cell tumors (SLCTs) in comparison to granulosa cell tumors (GCTs). METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were accessed and patients diagnosed with a malignant SLCT and GCT between 1988 and 2013 were selected. Demographic and clinico-pathological characteristics were compared using the Mann-Whitney and chi-square tests. Overall (OS) and cancer-specific survival (CSS) rates were estimated with the Kaplan-Meier method and compared with the log-rank test. Cox hazard models were constructed to control for confounders. RESULTS: A total of 175 and 1361 patients diagnosed with SLCT and GCT, respectively, were identified. Compared to patients with GCT, those with SLCT were younger (median age 32 vs. 51 years, p < 0.001) and more likely to present with larger tumors (median size 15 vs 9.5 cm, p < 0.001) confined to the ovary (77.5% vs 69.2%, p = 0.031). Patients with SLCTs had worse CSS compared to those with GCTs, p < 0.001 (5-year rate was 76.2% vs 90.7%). After controlling for the presence of extra-ovarian disease and tumor size (≤ 10 vs > 10 cm), SCLTs were associated with a worse cancer-specific mortality compared to GCTs. CONCLUSIONS: SLCTs are extremely rare, commonly arise in premenopausal patients. They are associated with a poorer prognosis compared to GCT.
Assuntos
Tumor de Células da Granulosa/epidemiologia , Neoplasias Ovarianas/epidemiologia , Tumor de Células de Sertoli-Leydig/epidemiologia , Adulto , Feminino , Tumor de Células da Granulosa/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Ovarianas/mortalidade , Tumor de Células de Sertoli-Leydig/mortalidade , Taxa de SobrevidaRESUMO
OBJECTIVES: Investigate the prevalence of bilateral salpingo-oophorectomy (BSO) for women ≤50 years with early stage low-grade endometrial stromal sarcoma (LGESS) and its impact on overall survival (OS). METHODS: Women ≤50 years, diagnosed with stage I LGESS and managed with hysterectomy between 2004 and 2015 were identified from the National Cancer Database. Patient demographics were recorded and compared with the chi-square test. OS for patients diagnosed between 2004 and 2014 with at least one month of follow-up was assessed using Kaplan-Meier curves, and compared with the log-rank test. RESULTS: A total 743 patients with a median age of 44 years met the inclusion criteria. Use of radiatiotherapy (9%), chemotherapy (0.8%) and hormonal therapy (11%) was infrequent. BSO was performed in 541 (72.8%) patients. Patients who had ovarian preservation (OP) were younger (median age 43 vs 45 years, p < 0.001), less likely to have comorbidities (6.9% vs 12.4%, p = 0.034), or undergo LND (30.7% vs 44.4%, p = 0.001). There were no differences between the two groups in terms of substage or patient race. Five year OS rates for patients who did (n = 490) and did not (n = 191) undergo BSO were 96.2% and 97.1% and there was no difference in OS, p = 0.50. Even after controlling for presence of comorbidities performance of BSO was not associated with better survival (HR: 1.28, 95% CI: 0.51, 3.19). CONCLUSIONS: Ovarian function was preserved in approximately one third of women ≤50 years with stage I LGESS with no clear detriment to overall survival. As BSO is associated with long term health effects in this patient population OP could be considered in selected women with stage I LGESS.
Assuntos
Salpingo-Ooforectomia/métodos , Sarcoma do Estroma Endometrial/cirurgia , Adolescente , Adulto , Bases de Dados Factuais , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Estudos Retrospectivos , Sarcoma do Estroma Endometrial/mortalidade , Análise de Sobrevida , Adulto JovemAssuntos
Doença Trofoblástica Gestacional , Mola Hidatiforme , Gonadotropina Coriônica , Feminino , Humanos , GravidezRESUMO
OBJECTIVE: To investigate the safety of uterine preservation in patients with high-grade epithelial ovarian carcinoma (EOC). STUDY DESIGN: The Surveillance, Epidemiology, and End Results database was accessed (1988-2014) and patients aged < = 45 years, diagnosed with an unilateral high-grade non-clear cell EOC confined to the ovary were selected. Based on surgery codes we determined whether hysterectomy was performed. Overall (OS) and cancer-specific survival (CSS) was estimated calculated following generation of Kaplan-Meier curves and compared using the log-rank test. Cox hazard model was constructed to control for possible confounders. RESULTS: A total of 1039 patients with a median follow-up of 119 months were identified. Rate of uterine preservation was 31.8 %. Patients who had hysterectomy were older (median 41 vs 32 yrs, p < 0.001). Patients with mucinous tumors were less likely to undergo hysterectomy (58.9 %) compared to those with endometrioid (73.9 %) and serous (75.9 %) carcinoma, p < 0.001. There was no difference in CSS between patients who did and did not have hysterectomy, p = 0.70 (5-yr rates were 93.9 % vs 92.2 %, respectively). After controlling for year of diagnosis, tumor histology (serous vs non-serous), disease stage, performance of lymph node dissection (LND) and tumor grade, uterine preservation was not associated with a worse cancer-specific (HR: 1.08, 95 % CI:0.69,1.71) and overall (HR:0.88, 95 % CI: 0.59, 1.32) mortality. CONCLUSION: In this retrospective cohort of patients with unilateral high-grade non-clear cell EOC confined to the ovary, uterine preservation was not associated with a worse prognosis.
Assuntos
Carcinoma Epitelial do Ovário/cirurgia , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Neoplasias Ovarianas/cirurgia , Adulto , Carcinoma Epitelial do Ovário/mortalidade , Feminino , Preservação da Fertilidade/métodos , Seguimentos , Humanos , Histerectomia/estatística & dados numéricos , Neoplasias Ovarianas/mortalidade , Sistema de Registros , Estudos RetrospectivosRESUMO
OBJECTIVE: To evaluate trends in the surgical management of young women and pediatric patients with malignant ovarian germ cell tumors (MOGCTs) and associated survival outcomes. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database we identified patients under 40 years who underwent surgery between 1994 and 2014. The Joinpoint Regression Program was employed to investigate the presence of temporal trends and calculate average annual percent change (AAPC) rates. For analysis purposes two age groups were formed; pediatric/adolescent (≤21 yrs) and young adult (22-40 yrs). Histology was categorized into dysgerminoma, immature teratoma, yolk-sac tumor, mixed germ cell tumor and other histology. Cancer specific survival was compared using log-rank tests. RESULTS: A total of 2238 patients were identified, with median age 21 years. Only 12.4% underwent hysterectomy. One third underwent omentectomy, and one half underwent lymphadenectomy (LND). A decrease in the rate of omentectomy (AAPC: -2.15, 95% CI: -3.4, -0.9) and hysterectomy (AAPC: -3.31, 95% CI: -6.1, -0.4) was observed. There was no change in the rate of LND (AAPC: 0.17, 95% CI: -0.7, 1.1). Pediatric patients were less likely to undergo omentectomy (30.2% vs 35.5%, p < 0.001), hysterectomy (3.5% vs 22%, p < 0.001) and LND (45.6% vs 54.7%, p < 0.001). There were no apparent survival differences according to the performance of hysterectomy, omentectomy or LND, when stratified by early (stage I) and advanced stage (II-IV), (p > 0.05). CONCLUSIONS: Pediatric patients with MOGCTs undergo less extensive surgical staging. A trend towards less extensive surgical procedures for young women over time was observed, without an apparent detrimental effect on cancer specific survival.
Assuntos
Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Ovarianas/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Procedimentos Cirúrgicos de Citorredução/métodos , Procedimentos Cirúrgicos de Citorredução/tendências , Disgerminoma/patologia , Disgerminoma/cirurgia , Tumor do Seio Endodérmico/patologia , Tumor do Seio Endodérmico/cirurgia , Feminino , Humanos , Histerectomia/métodos , Histerectomia/tendências , Lactente , Excisão de Linfonodo , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Sistema de Registros , Programa de SEER , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To estimate the incidence of gestational trophoblastic neoplasia following complete and partial molar pregnancy after reaching normal human chorionic gonadotropin (hCG) levels to guide evidence-based follow-up recommendations. DATA SOURCES: MEDLINE, EMBASE, Web of Science, POPLINE, Cochrane, and ClinicalTrials.gov were searched from inception to November 2018, using the intersection of "gestational trophoblastic disease," "molar pregnancy," and "human chorionic gonadotropin" themes. METHODS OF STUDY SELECTION: Search results were screened to identify cohort studies of molar pregnancy reporting gestational trophoblastic neoplasia development, with at least 6 months of intended normal hCG follow-up. TABULATION, INTEGRATION, AND RESULTS: Two reviewers independently identified articles for inclusion. Data were extracted using a standardized form. For meta-analysis, cumulative incidence of gestational trophoblastic neoplasia, with CIs by the Agresti-Coull method, and pooled risk ratios (RRs) comparing complete and partial mole were calculated. Among the 19 eligible studies that reported adequate data for inclusion in the primary meta-analysis, we found low incidence of gestational trophoblastic neoplasia after normal hCG level following both complete mole (64/18,357, 0.35%, 95% CI 0.27-0.45%), and partial mole (5/14,864, 0.03%, 95% CI 0.01-0.08%). There was a significantly higher risk of gestational trophoblastic neoplasia after complete compared with partial molar pregnancy (RR 4.72, 95% CI 1.81-12.3, P=.002). Among gestational trophoblastic neoplasia cases after normal hCG level following complete mole, 89.6% occurred when the time from evacuation to normalization was 56 days or longer, and 60.7% were diagnosed beyond the commonly recommended 6-month surveillance interval. Sensitivity analyses, including those limiting to studies at low risk of bias, did not significantly affect results. We found an overall incidence of gestational trophoblastic neoplasia of 15.7% for complete mole (1,354/8,611, 95% CI 15.0-16.5%) and 3.95% for partial mole (221/5,593, 95% CI 3.47-4.50%). CONCLUSION: Gestational trophoblastic neoplasia development after normal hCG level following molar pregnancy is rare. Recommendations for frequency and duration of hCG follow-up can be minimized to lessen burden on patients and informed by the type of molar pregnancy and time interval from uterine evacuation to hCG normalization. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42019116414.
Assuntos
Doença Trofoblástica Gestacional/epidemiologia , Mola Hidatiforme/cirurgia , Neoplasias Uterinas/cirurgia , Curetagem a Vácuo , Gonadotropina Coriônica/sangue , Feminino , Humanos , Mola Hidatiforme/sangue , Mola Hidatiforme/patologia , Incidência , Gravidez , Fatores de Risco , Neoplasias Uterinas/sangue , Neoplasias Uterinas/patologiaRESUMO
BACKGROUND/AIM: We evaluated the incidence of uterine and breast cancer among women diagnosed with granulosa cell tumors (GCTs) of the ovary. PATIENTS AND METHODS: The US Surveillance, Epidemiology, and End Results (SEER) database was accessed and patients diagnosed with a GCT and had a known follow-up between 1973-2014 were identified. Personal tumor history was extracted and patients with a previous or subsequent malignant breast or uterine tumor were identified. The expected incidence of breast and uterine cancer was calculated based on the U.S age-specific rate of breast and uterine cancer per 100,000 women. Standardized incidence ratio (SIR) with 95% confidence intervals (95% CI) were calculated for each tumor. RESULTS: A total of 1908 cases of GCT were identified. Seventy- nine (4.14%) and 53 (2.78%) patients were diagnosed with a malignant breast and uterine malignancy. The cumulative expected number of malignant breast and uterine tumors was 27 (1.41%) and 6 (0.31%), respectively. The calculated SIR for breast and uterine malignancies was 2.96 (95%CI=2.34, 3.68) and 8.83 (95%CI=6.61, 11.56), respectively. CONCLUSION: An increased incidence of breast and uterine malignancies among patients diagnosed with GCTs was observed.
Assuntos
Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Tumor de Células da Granulosa/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias Uterinas/epidemiologia , Neoplasias Uterinas/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Programa de SEER , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To investigate the prognostic significance of elevated pre-operative serum CA-125 values for patients with early stage ovarian sex cord - stromal tumors (SCSTs). METHODS: Patients diagnosed between 2004 and 2015 with a SCST were drawn from the U.S National Cancer Database. Those with stage I disease, and normal or elevated CA-125 values were selected for further analysis. Overall survival (OS) was evaluated for patients diagnosed between 2004 and 2014 with Kaplan-Meier curves, and compared with the log-rank test. A multivariate Cox analysis was performed to control for known confounders. RESULTS: A total of 1156 patients met the inclusion criteria; 486 (42%) had elevated pre-treatment CA-125 values. Patients with elevated pre-treatment CA-125 (n = 417) had worse OS compared to those with normal values (n = 588), p < 0.001 from log-rank test; 5-yr OS rates were 86.8% and 94.8% respectively. After controlling for patient age (<50 vs > = 50 yrs), the presence of medical co-morbidities, tumor histology (granulosa vs non-granulosa), size (<10 vs > = 10 cm vs unknown) and the performance of lymphadenectomy, elevated pre-treatment CA-125 levels were associated with a worse survival (HR: 1.80, 95% CI: 1.15, 2.82, p = 0.01). CONCLUSIONS: In a large cohort of patients with early stage SCSTs elevated preoperative CA-125 levels were associated with worse survival.
Assuntos
Antígeno Ca-125/sangue , Neoplasias Ovarianas/sangue , Tumores do Estroma Gonadal e dos Cordões Sexuais/sangue , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/mortalidade , Prognóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/mortalidade , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: The aim of this study was to investigate the patterns of use and outcomes of adjuvant chemotherapy for patients diagnosed with FIGO stage I ovarian clear cell carcinoma (OCCC). METHODS: A cohort of patients diagnosed between 2004 and 2015 with OCCC was drawn from the National Cancer Database. Those with stage I disease who had primary surgery and underwent systematic lymphadenectomy (defined as at least 10 lymph nodes removed) were selected for further analysis. Factors associated with the administration of adjuvant chemotherapy were investigated with multivariate logistic regression. Overall survival (OS) was evaluated using Kaplan-Meier curves for patients diagnosed between 2004 and 2014, while comparisons were made with the log-rank test. Multivariate Cox analysis was performed to control for possible confounders. RESULTS: A total of 2325 patients met the inclusion criteria. Median age was 55â¯years. The majority were White (86.6%). Adjuvant chemotherapy was administered to 1839 (79.1%) patients. Hospital type and location, patient age, disease sub-stage, and year of diagnosis were independently associated with the administration of chemotherapy. Patients who received adjuvant chemotherapy (nâ¯=â¯1629) had better OS than those who did not (nâ¯=â¯443), (5-year OS rates 89.2% vs 82.6%, pâ¯<â¯0.001). After controlling for disease sub-stage, age, race, hospital type and medical comorbidities, adjuvant chemotherapy was associated with better overall survival (HR: 0.59, 95% CI: 0.45, 0.78). CONCLUSIONS: Adjuvant chemotherapy could be associated with a survival benefit for patients with stage I OCCC.
Assuntos
Adenocarcinoma de Células Claras/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Carcinoma Epitelial do Ovário , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologiaRESUMO
PURPOSE: To evaluate the prevalence of regional lymph node (LN) metastasis in patients with non-clear cell epithelial ovarian cancer apparently confined to the ovary, stratified by tumor grade. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was accessed (1988-2014). We identified patients with epithelial ovarian carcinoma of serous, endometrioid and mucinous histology apparently confined to the ovary who underwent extensive lymphadenectomy (defined as at least 20 lymph nodes removed). Demographics, tumor histology, grade and lymph node status were collected. Comparisons were made with Chi square and Mann-Whitney U tests. RESULTS: A total of 1242 women met the inclusion criteria. Endometrioid adenocarcinoma was the most common histology (564 patients (45.4%)) while 443 (35.7%) and 235 (18.9%) patients had serous, and mucinous adenocarcinoma, respectively. The rate of LN metastasis in low-grade serous was 9.0% (6/67) vs. 14.4% (54/376) in high-grade serous histology (OR, 1.71, 95% CI 0.70, 4.14, p = 0.24). In patients with low-grade endometrioid tumors, the rate of LN metastasis was 1.7% (7/407) vs. 5.1% (8/157) observed in those with high-grade tumors (OR: 3.07, 95% CI 1.09, 8.61, p = 0.033). Lastly, the rate of LN metastasis in mucinous histology was 1.7% (3/177) in low-grade vs. 8.6% (5/58) in high-grade tumors (OR: 5.47, 95% CI 1.27, 23.66, p = 0.024). CONCLUSIONS: Regional LN metastasis in apparent stage I low-grade mucinous and endometrioid ovarian tumors is infrequent.
Assuntos
Excisão de Linfonodo/métodos , Linfonodos/patologia , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Adulto JovemRESUMO
Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is an uncommon cause of adrenal Cushing syndrome (CS) in which cortisol and occasionally other steroid hormones can be secreted under the influence of aberrantly expressed G-protein coupled receptors (GPCRs) in the adrenal cortex. We describe the unique case of a 64-year-old postmenopausal female with PBMAH whose adrenal lesions expressed luteinizing hormone receptors (LHr). She presented initially with CS and underwent right adrenalectomy; a few years later she presented with macromastia and mastodynia, possibly due to estrogen excess from her remaining left adrenocortical masses. Testing before and after treatment with quarterly leuprolide acetate therapy and immunohistochemistry on tissue and targeted sequencing of the genes of interest were performed. Tissue from the patient's right adrenal was tested for P450 aromatase (CYP19A1) and LHr expression; both were expressed throughout the hyperplastic cortex, although expression was more intense in the adenomatous areas. Targeted sequencing revealed a pathogenic PDE11A mutation, as well as variants in the ARMC5 and INHA genes. PDE11A expression was decreased in the adenoma but there was no loss of heterozygosity for the PDE11A locus. Because of the clinical presentation and LHr expression, quarterly leuprolide acetate therapy was started. Shortly after initiation of therapy, the patient reported decreased breast size and pain; she remains well controlled to date, after 10 years of treatment. This is the first description of a patient with PBMAH presenting with severe macromastia and mastodynia from what appears to be excess estrogen production from her adrenal tumor. The patient had a long-lasting response to chronic leuprolide acetate treatment, showing that drug therapy exploiting the aberrant receptor expression in PBMAH is possible even in the absence of cortisol overproduction.
Assuntos
Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Estrogênios/metabolismo , Leuprolida/uso terapêutico , 3',5'-GMP Cíclico Fosfodiesterases , Hiperplasia Suprarrenal Congênita/diagnóstico por imagem , Idoso , Sequência de Bases , Seguimentos , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Diester Fosfórico Hidrolases/genética , Receptores do LH/genética , Análise de Sequência de DNA , Coloração e Rotulagem , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
CONTEXT: Germline mutations in genes coding succinate dehydrogenase (SDH) subunits A, B, C, and D have been identified in familial paragangliomas (PGLs)/pheochromocytomas (PHEOs) and other tumors. We described a GH-secreting pituitary adenoma (PA) caused by SDHD mutation in a patient with familial PGLs. Additional patients with PAs and SDHx defects have since been reported. DESIGN: We studied 168 patients with unselected sporadic PA and with the association of PAs, PGLs, and/or pheochromocytomas, a condition we named the 3P association (3PAs) for SDHx germline mutations. We also studied the pituitary gland and hormonal profile of Sdhb(+/-) mice and their wild-type littermates at different ages. RESULTS: No SDHx mutations were detected among sporadic PA, whereas three of four familial cases were positive for a mutation (75%). Most of the SDHx-deficient PAs were either prolactinomas or somatotropinomas. Pituitaries of Sdhb(+/-) mice older than 12 months had an increased number mainly of prolactin-secreting cells and several ultrastructural abnormalities such as intranuclear inclusions, altered chromatin nuclear pattern, and abnormal mitochondria. Igf-1 levels of mutant mice tended to be higher across age groups, whereas Prl and Gh levels varied according to age and sex. CONCLUSION: The present study confirms the existence of a new association that we termed 3PAs. It is due mostly to germline SDHx defects, although sporadic cases of 3PAs without SDHx defects also exist. Using Sdhb(+/-) mice, we provide evidence that pituitary hyperplasia in SDHx-deficient cells may be the initial abnormality in the cascade of events leading to PA formation.
Assuntos
Adenoma/genética , Neoplasias das Glândulas Suprarrenais/genética , Paraganglioma/genética , Feocromocitoma/genética , Neoplasias Hipofisárias/genética , Succinato Desidrogenase/genética , Adolescente , Adulto , Idoso , Animais , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Mutação em Linhagem Germinativa , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Adulto JovemRESUMO
The cAMP-dependent protein kinase A (PKA) signaling system is widely expressed and has a central role in regulating cellular metabolism in all organ systems affected by obesity. PKA has four regulatory (RIα, RIIα, RIß, RIIß) and four catalytic (Cα, Cß, Cγ, Prkx) subunit isoforms that have tissue-specific expression profiles. In mice, knockout (KO) of RIIß, the primary PKA regulatory subunit in adipose tissue or knockout of the catalytic subunit Cß resulted in a lean phenotype that resists diet-induced obesity and associated metabolic complications. Here we report that the disruption of the ubiquitously expressed PKA RIIα subunit in mice (RIIαKO) confers resistance to diet-induced obesity, glucose intolerance, and hepatic steatosis. After 2-week high-fat diet exposure, RIIαKO mice weighed less than wild-type littermates. Over time this effect was more pronounced in female mice that were also leaner than their wild-type counterparts, regardless of the diet. Decreased intake of a high-fat diet contributed to the attenuated weight gain in RIIαKO mice. Additionally, RIIα deficiency caused differential regulation of PKA in key metabolic organs: cAMP-stimulated PKA activity was decreased in liver and increased in gonadal adipose tissue. We conclude that RIIα represents a potential target for therapeutic interventions in obesity, glucose intolerance, and nonalcoholic fatty liver disease.