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1.
Antonio González Martín Amit M. Oza Andrew C. Embleton Jacobus Pfisterer Jonathan A. Ledermann Eric Pujade-Lauraine Gunnar Kristensen Monique A. Bertrand Philip Beale Andrés Cervantes Emma Kent Richard S. Kaplan Mahesh K.B. Parmar Nana Scotto Timothy J. Perren 《Gynecologic oncology》2019,152(1):53-60
Objective
In the randomized phase 3 ICON7 trial (ISRCTN91273375), adding bevacizumab to chemotherapy for newly diagnosed ovarian cancer significantly improved progression-free survival (PFS; primary endpoint) but not overall survival (OS; secondary endpoint) in the intent-to-treat (ITT) population. We explored treatment effect according to stage and extent of residual disease.Methods
Patients with stage IIB–IV or high-risk (grade 3/clear-cell) stage I–IIA ovarian cancer were randomized to receive six cycles of carboplatin and paclitaxel either alone or with bevacizumab 7.5?mg/kg every 3?weeks followed by single-agent bevacizumab for 12 further cycles (total duration 12?months). Post hoc exploratory analyses of subgroups defined by stage and extent of residual disease at diagnosis within the stage IIIB–IV population (European indication) was performed.Results
The PFS benefit from bevacizumab was seen consistently in all subgroups explored. The PFS hazard ratio was 0.77 (95% confidence interval [CI], 0.59–0.99) in 411 patients with stage IIIB–IV ovarian cancer with no visible residuum and 0.81 (95% CI, 0.69–0.95) in 749 patients with stage IIIB–IV disease and visible residuum. As in the ITT population, no OS difference was detected in any subgroup except the previously described ‘high-risk’ subgroup. Safety results in analyzed subgroups were consistent with the overall population.Conclusions
Adding bevacizumab to front-line chemotherapy improves PFS irrespective of stage/residual disease. In patients with stage III with >1?cm residuum, stage IV or inoperable disease, this translates into an OS benefit. No OS benefit or detriment was seen in other subgroups explored. 相似文献2.
Objective
It is unclear if the types of surgical procedures performed on long-term survivors (LTS) of high-grade serous ovarian carcinoma (HGSOC) contribute to prolonged survival. In this case-control study we review the surgical procedures performed on LTS and describe their individual longitudinal disease courses.Methods
Women with FIGO stage III–IV high-grade serous cancer of the ovary, fallopian tube or peritoneum were selected from the University of Chicago ovarian cancer database. LTS were those surviving >7?years and controls were short-term survivors (STS) living 1–2?years. Patients with non-serous histology, low grade, and low malignant potential tumors were excluded.Results
We identified 450 women with stage III/IV HGSOC including 45 LTS and 78 STS. LTS showed a trend towards lower disease burden, yet underwent more aggressive surgical treatment. Interestingly, only 15 LTS (34%) were debulked to microscopic disease and 9 LTS (21%) underwent suboptimal debulking. Two LTS (5%) recurred within 12?months. LTS had heterogeneous clinical courses with 13 (29%) never experiencing a recurrence with 143?months median follow-up and 32 (71%) experiencing a recurrence with 115?months median follow-up. Of the women who recurred, 19 (59%) underwent at least one surgery for recurrence.Conclusions
Aggressive surgical treatment intended to achieve microscopic disease, primary debulking surgery, preservation of sensitivity to chemotherapy, and recurrence amenable to secondary debulking are associated with long-term survival. However, clinicopathologic data are insufficient to predict long-term survival of HGSOC. Biologic characterization of these patient's tumors likely holds the key to understanding their unusually favorable courses. 相似文献3.
Clémence Romeo Florence Joly Isabelle Ray-Coquard Claude El Kouri Anne Mercier-Blas Dominique Berton-Rigaud Elsa Kalbacher Oana Cojocarasu Michel Fabbro Jacques Cretin Alain Zannetti Sophie Abadie-Lacourtoisie Delphine Mollon Anne-Claire Hardy-Bessard Magali Provansal Emmanuel Blot Catherine Delbaldo Anne Lesoin Benoît You 《Gynecologic oncology》2019,152(1):68-75
Background
Carboplatin and pegylated liposomal doxorubicin combination is a standard regimen in platinum-sensitive recurrent ovarian cancer patients. The pegylated liposomal doxorubicin shortage from 2011 to 2013 urged assessment of the efficacy and tolerance of non-pegylated liposomal doxorubicin in combination with carboplatin.Methods
MYCA was a multicenter 2-step phase Ib-II single arm trial meant to assess the safety and efficacy of carboplatin AUC 5?mg/min.mL combined with non-pegylated liposomal (dose escalation from 40 to 50?mg/m2 during phase Ib step; and 50?mg/m2 during phase II step), every 4?weeks in patients with platinum-sensitive relapse. The primary objective was disease control rate (DCR) at 12?months.Results
From 2012 to 2014, 87 patients were enrolled. They were treated as second (78%) or third line (22%) treatment. Total of 67 patients (78%) completed 6?cycles. G-CSF support was prescribed to 58% patients. The DCR at 12?months was 30.0% (95% CI, 20.3–39.7); the median PFS was 10.0?months (95% CI, 8.6–11.0). The median overall survival was 28.1?months (95% CI, 22.3–32.5); and the objective response rate was 58% (95% CI, 47–68). Grade 3–4 neutropenia, anemia and thrombocytopenia were observed in 17%, 13% and 1%, respectively; febrile neutropenia in 6%. One patient who did not receive GCSF support died from febrile neutropenia.Conclusion
Non-pegylated liposomal doxorubicin-carboplatin combination exhibits an acceptable safety profile, with GCSF prophylaxis. Acknowledging the lack of direct comparison, efficacy in terms of 12?month DCR was comparable with standard treatments. 相似文献4.
Diogo Torres Amanika Kumar Jamie N. Bakkum-Gamez Amy L. Weaver Michaela E. McGree Chen Wang Carrie L. Langstraat William A. Cliby 《Gynecologic oncology》2019,152(2):223-227
Objective
To evaluate the contribution of molecular subtype to 30-day postoperative complications and 90-day mortality after primary debulking surgery (PDS) in advanced stage high-grade serous ovarian cancer (HGSOC).Methods
Patients with stages III–IV HGSOC undergoing PDS from 1994 to 2011 with available molecular subtyping were included. Residual disease (RD) status was categorized as 0, 0.1–0.5, 0.6–1.0, or >1?cm. Surgical complexity scores were calculated as high, intermediate, or low as previously published. Postoperative complications were graded according to the modified Accordion classification 0–4 scale; severe was defined as grade ≥3. Molecular subtypes were derived from Agilent 4?×?44k tumor mRNA expression profiles and categorized as mesenchymal (MES) or non-mesenchymal (non-MES). Logistic regression modeling was used to assess associations.Results
Of 329 patients, 68.7% were stage IIIC, 80.5% had RD ≤1?cm, 28.0% had MES subtype, and 19.5% had a grade 3–4 complication; 90-day mortality was 5.8%. In univariate analysis, patients with MES subtype were more likely to have severe complications compared to non-MES (31.5 vs. 14.8%; OR 2.66, 95% CI 1.51–4.69; p?<?0.001). MES subtype remained an independent predictor of complications (adjusted OR 2.14, 95% CI 1.17–3.92; p?=?0.01) in a multivariable model which included ASA score, preoperative albumin, and surgical complexity. There was no statistical difference in 90-day mortality in patients with MES compared to non-MES subtype (7.6 vs. 5.1%; OR 1.54, 95% CI 0.59–4.05; p?=?0.38).Conclusions
MES subtype is an independent predictor of severe postoperative morbidity and adds to the potential use of pre-operative molecular testing in planning primary treatment of patients with advanced ovarian cancer. 相似文献5.
Background
Epithelial ovarian cancer (EOC) is still a major gynecologic problem with poor 5 year survival rate due to distance metastases, despite routine surgery and chemotherapy. The precise underlying molecular mechanisms that trigger EOC migration and invasion are unclear. Recent studies suggest that the expression of microRNAs is widely dysregulated in ovarian cancer; and that they have evolved into tumorigenic processes, including cell proliferation, apoptosis and motility.Methods
The expression of miR-124 was assessed in clinical ovarian cancer specimens and cell lines using miRNA qRTPCR. The function of miR-124 on cell migration and invasion was confirmed in vitro through wound healing assay and transwell assay. Luciferase reporter assay was used to confirm target associations.Results
We showed that miR-124 is down-regulated in ovarian cancer specimens as well as in cell lines; and that low-level expression of miR-124 is much lower in highly metastatic ovarian cancer cells and tissues. Meantime, overexpression of miR-124 dramatically inhibits the motility of ovarian cancer cells in vitro and substantially suppresses the protein expression of SphK1, reported as an invasion and metastasis-related gene in human cancers, whose expression is markedly increased in both ovarian cancer cell lines and clinical samples, particularly in two highly metastasis cells, SKOV3-ip and HO8910pm as well as metastatic ovarian tumor tissues. Furthermore, SphK1 is identified as a direct target of miR-124, and knock-down of SphK1 in ovarian cancer cells, SKOV3-ip and HO8910pm, could mimic the inhibition of migration and invasion by miR-124, while re-introduction of SphK1 abrogates the suppression of motility and invasiveness induced by miR-124 in both cell lines.Conclusions
Our studies suggest a protective role of miR-124 in inhibition of migration and invasion in the molecular etiology of ovarian cancer, and a potentially novel application of miR-124 in the regulation of migration and invasion in EOC.6.
Qian Zhong Zhongyi Hu Qiao Li Tao Yi Jinke Li Hanshuo Yang 《Gynecologic oncology》2019,152(1):157-165
Objective
Poly(ADP-ribose) polymerase inhibitors (PARPi) are active in cancer cells that have impaired repair of DNA by the homologous recombination (HR) pathway. Strategies that disrupt HR may sensitize HR-proficient tumors to PARP inhibition. As a component of the core cell cycle machinery, cyclin D1 has unexpected function in DNA repair, suggesting that targeting cyclin D1 may represent a plausible strategy for expanding the utility of PARPi in ovarian cancer.Methods
BRCA1 wildtype ovarian cancer cells (A2780 and SKOV3) were treated with a combination of CCND1 siRNA and olaparib in vitro. Cell viability was assessed by MTT. The effects of the combined treatment on DNA damage repair and cell cycle progression were examined to dissect molecular mechanisms. In vivo studies were performed in an orthotopic ovarian cancer mouse model. Animals were treated with a combination of lentivirus-mediated CCND1 shRNA and olaparib or olaparib plus scrambled shRNA. Molecular downstream effects were examined by immunohistochemistry.Results
Silencing of cyclin D1 sensitized ovarian cancer cells to olaparib through interfering with RAD51 accumulation and inducing cell cycle G0/G1 arrest. Treatment of lentivirus-mediated CCND1-shRNA in nude mice statistically significantly augmented the olaparib response (mean tumor weight?±?SD, CCND1-shRNA plus olaparib vs scrambled shRNA plus olaparib: 0.172?±?0.070?g vs 0.324?±?0.044?g, P<?0.05).Conclusions
Silencing of cyclin D1 combined with olaparib may lead to substantial benefit for ovarian cancer management by mimicking a BRCAness phenotype, and induction of G0/G1 cell cycle arrest. 相似文献7.
Objective
Neoadjuvant chemotherapy (NAC) has been shown to be noninferior to primary surgery in advanced stage ovarian cancer. We examined the impact of the neoadjuvant approach in patients with optimal residuals (<1?cm).Methods
Retrospective review of optimally debulked stage 3/4 ovarian cancer was performed. Chi-square tests were used to detect significant associations between categorical variables. A Cox regression model was built to predict patients' overall survival, adjusting for age, tumour grade, histology, use of adjuvant intraperitoneal chemotherapy, residual status, and primary treatment modality.Results
One hundred one patients were reviewed. Median age was 60.5 (range 39–85). NAC was used in 34 patients. Serous histology was documented in 60 of 101 patients (59%). Microscopic residuals were achieved in 70 patients (69%). There was no significant association between primary treatment modality and microscopic residuals status. With a median follow-up time of 33 months, progression was observed in 53% of patients, with a median progression-free survival of 19.4 months. The use of NAC was an independent adverse prognostic factor (hazard ratio 5.79; 95% CI 2.15–15.55, P?=?0.001) for overall survival. Macroscopic residual was an independent adverse prognostic factor (hazard ratio 10.76; 95% CI 2.98–38.89, P?<?0.001). The overall Kaplan-Meier median survival estimate was 54.5 months (95% CI 50.64–58.36) in the primary surgery group compared with 41.43 months (95% CI 35.58–47.29) in those given NAC (P?=?0.002)Conclusion
Primary surgery should be the preferred approach in patients with an initial high likelihood of being optimally cytoreduced. 相似文献8.
Gulisa Turashvili Natalia R. Gómez-Hidalgo Jessica Flynn Mithat Gonen Mario M. Leitao Robert A. Soslow Rajmohan Murali 《Gynecologic oncology》2019,152(1):38-45
Objective
Determining whether carcinomas concurrently involving endometrium and ovary are independent primary tumors (IPTs) or endometrial carcinomas with ovarian metastases (at least stage IIIA endometrial cancers, IIIA-EC) using clinicopathologic criteria is often challenging. Recent genomic studies showed that most such tumors are clonally related. We sought to identify clinicopathologic features associated with clinical outcomes, and to separate women with these tumors into clinically low-risk and high-risk groups.Methods
We reviewed clinical and pathologic data from 74 women who, between 1993 and 2014, underwent primary surgery for endometrial cancer and had concurrent ovarian involvement.Results
The endometrial carcinomas were endometrioid (EECs, n?=?41) or non-endometrioid (ENECs, n?=?33). Nineteen (26%) cases were originally classified as IPTs using clinicopathologic criteria. Multivariate analysis revealed that lymph node involvement (hazard ratio (HR)?=?2.38, 95% CI 1.13–5.02, p?=?0.023) and non-endometrioid endometrial tumor histology (HR?=?6.27, 95% CI 2.6–15.13, p?<?0.001) were associated with poorer progression-free survival (PFS). Multivariate analysis of 65 women with known lymph node status revealed two prognostically distinct groups: a high-risk group comprising ENECs with ≥50% myometrial invasion irrespective of lymph node status (n?=?21; median PFS 12.7?months, 95% CI, 9.24–19.8); and a low-risk group consisting of all EECs, as well as lymph node-negative ENECs with <50% myometrial invasion (n?=?44, median PFS not reached). The risk-based classification was superior to the original classification of endometrial cancers as IPTs vs. IIIA-EC for predicting PFS (log-rank test, p?<?0.001 vs. p?=?0.07).Conclusion
Our proposed risk-based stratification enables categorization of women with concurrent endometrial and ovarian tumors according to their likely clinical outcomes. 相似文献9.
Yair Daykan Rona Bogin Merav Sharvit Zvi Klein Dana Josephy Meir Pomeranz Nissim Arbib Tal Biron-Shental Ron Schonman 《Journal of minimally invasive gynecology》2019,26(1):117-121
Study Objective
To investigate the pregnancy and neonatal outcomes of surgical treatment for adnexal torsion (AT) during pregnancy.Design
A retrospective case-control study (Canadian Task Force classification II-2).Setting
A tertiary care academic medical center.Measurements and Main Results
The study group included all parturients who underwent surgery for suspected AT during pregnancy from January 2005 to January 2017. The control group included parturients with an uneventful pregnancy matched by maternal age, parity, multiple gestation, and pregnancy complications. The primary outcome was gestational age at delivery. Secondary outcomes were perinatal outcomes and intraoperative and immediate postoperative complications. Among 85 study group patients with suspected AT, 78 (91.7%) underwent laparoscopy and 7 (8.3%) laparotomy. Torsion was diagnosed in 84 patients (98.8%). The gestational age at delivery was similar between the study and control groups (38.7?±?1.5 vs 38.6?±?1.6 weeks, respectively; p?=?.908) as was preterm labor (5.8% in both groups, p?=?1.00). There was no significant difference between the study and control groups in pregnancy and neonatal outcomes, including Apgar scores, mean cord blood pH (7.25?±?0.1 and 7.26?±?0.08, respectively), and birth weight (3040?±?473?g and 3115?±?584?g, respectively). In the study group, the mean gestational age at surgery was 11.2?±?6 weeks (range, 4–34 weeks). The average operative time was 40.2?±?22 minutes. In the postoperative follow-up, 3 (3.5%) patients had a first trimester miscarriage. A previous cesarean delivery was a risk factor for ovarian torsion during pregnancy (p?=?.012).Conclusion
Adnexal detorsion with or without additional surgical procedures during pregnancy did not affect the gestational age at delivery and did not appear to increase fetal or maternal complication rates. 相似文献10.
Andrea Varga Sarina Piha-Paul Patrick A. Ott Janice M. Mehnert Dominique Berton-Rigaud Anne Morosky Ping Yang Jane Ruman Daniela Matei 《Gynecologic oncology》2019,152(2):243-250
Objective
To evaluate safety, tolerability, and antitumor activity of pembrolizumab monotherapy in patients with programmed death ligand 1 (PD-L1)–expressing advanced ovarian cancer enrolled in the multicohort, phase Ib KEYNOTE-028 trial.Methods
Key inclusion criteria were age ≥18?years; advanced ovarian epithelial, fallopian tube, or primary peritoneal carcinoma; failure of previous therapy; and tumor PD-L1 positivity. Patients received pembrolizumab (10?mg/kg every 2?weeks) for ≤24?months or until disease progression/intolerable toxicity. Tumor response was assessed per RECIST v1.1 (investigator review). Adverse events (AEs) were graded using CTCAE version 4.0. Primary end point was confirmed objective response rate (ORR) per RECIST v1.1 (investigator review); data cutoff date was February 20, 2017.Results
Twenty-six patients (median age, 57.5?years) with PD-L1–positive advanced metastatic ovarian cancer received pembrolizumab; 38.5% had metastatic disease, and 73.1% previously received ≥3 lines of therapy. Treatment-related AEs (TRAEs) occurred in 19 (73.1%) patients, most commonly arthralgia (19.2%), nausea (15.4%), and pruritus (15.4%). One grade 3 TRAE (increased plasma transaminase level) occurred. No deaths and no treatment discontinuations due to TRAEs occurred. After a median follow-up duration of 15.4?months, ORR was 11.5% (1 complete response, 2 partial responses); 7 patients (26.9%) achieved stable disease. Median progression-free and overall survival were 1.9 (95% CI, 1.8–3.5) and 13.8 (95% CI, 6.7–18.8) months, respectively.Conclusion
Pembrolizumab conferred durable antitumor activity with manageable safety and toxicity in patients with advanced PD-L1–positive ovarian cancer and is under further investigation in an ongoing phase II trial, KEYNOTE-100. 相似文献11.
V. Rodriguez-Freixinos L. Fariñas-Madrid M. Gil-Martin P. Barretina-Ginesta M. Romeo G. Villacampa B. Pardo H. Ahmed S. Recalde J.M. Piulats M.C. Gómez-Plaza A. Gil-Moreno E. Sala S. Martínez-Román J. Ponce C. Meléndez E. Carballas R. Dientsmann A. Oaknin 《Gynecologic oncology》2019,152(2):270-277
Objectives
The hallmarks of germline(g) and/or somatic(s) BRCA1/2 mutation ovarian cancer (BMOC) patients are increased sensitivity to platinum-based chemotherapy (PCT) and PARP inhibitors (PARPi). There is little information on the effectiveness of chemotherapy in heavily pretreated (≥3 CT lines) g/sBMOC patients.Methods
g/sBMOC patients who received CT from 2006 to 2016 at 4 cancer centers in Spain were selected. Overall survival (OS) and time to progression (TTP) were calculated with Kaplan Meier and Cox models.Results
135?g/sBMOC patients were identified (6% sBRCA1/2 mutations). The median number of chemotherapy lines was 2 (1–7). The 6-years OS rate was 69.4% and 71% in BRCA1 or BRCA2 mutation carriers (p?=?0.98). A total of 57 (42%) patients had ≥3 CT lines (3–7), which encompassed a total of 155 treatments. The median overall TTP across all treatment lines beyond 2nd line was 10.2?months (CI 95% 8.4–11.9?months). In the platinum-sensitive setting, TTP was improved with PCT plus PARPi (17.1?m), PCT (12.6?m) or PARPi (12.4?m) versus non-PCT (4.9?m; p?<?0.001 all comparisons). In the platinum-resistant setting, these differences in TTP were not statistically significant. A multivariate model confirmed that primary platinum-free interval (PFI)?>?12?months and exposure to PCT and PARPi associated with improved outcomes. PARPi exposure did not compromise benefit of subsequent CT beyond 2nd relapse.Conclusions
Heavily pretreated g/sBMOC demonstrated CT sensitivity, including for non-PCT choices. Primary platinum-free interval (PFI) >12?months and exposure to both platinum-based chemotherapy and PARPi associate with improved prognosis in heavily pretreated g/sBMOC patients. 相似文献12.
Sara Wiswell Jeffrey G. Bell Jennifer McHale John O. Elliott Kellie Rath Aine Clements 《Gynecologic oncology》2019,152(2):334-338
Objectives
Most art therapy research has involved patients with malignancies other than gynecologic cancer. The current study aimed to assess the impact of an art therapy intervention on the quality of life (QOL) in patients with gynecologic cancer who were receiving chemotherapy.Methods
This was a prospective, non-randomized, pilot study. Eligible patients had a primary or recurrent gynecologic malignancy scheduled to be treated with at least 6?cycles of chemotherapy over 18?weeks. The intervention consisted of five sessions of art therapy during the chemotherapy. Patients completed a Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire prior to starting chemotherapy, and again at completion of the fifth session. Differences between the FACT-G scores were examined by paired t-tests. An increase in the mean FACT-G score indicated an improvement in QOL. At each session, the patients completed a separate, supplemental questionnaire to subjectively rate the benefit of the session and to express their experience with the art intervention.Results
Twenty-four patients enrolled. Eight did not complete the study, leaving 16 evaluable patients. The mean FACT-G score pre-chemotherapy was 82.3 (95% CI: 75.5, 89.2), and post-art therapy was 78.6 (95% CI: 71.7, 85.5). The mean change in QOL was ?3.7 points (95% CI: ?10.7, 3.2, p?=?0.270). A supplemental questionnaire indicated that 15 of 16 patients felt that art therapy was beneficial at each session.Conclusions
FACT-G scores did not significantly change over the course of chemotherapy in patients with gynecologic cancers receiving art therapy. Several published studies have indicated that chemotherapy is associated with a decline in QOL. Our results suggest art therapy may help to prevent or mitigate this decline. 相似文献13.
L. Tortorella J. Casarin K.C. Mara A.L. Weaver F. Multinu G.E. Glaser W.A. Cliby G. Scambia A. Mariani A. Kumar 《Gynecologic oncology》2019,152(1):151-156
Objective
Pelvic exenteration (PE) is an extensive surgery associated with high rates of postoperative morbidity and mortality. The absence of well-defined preoperative selection criteria to identify patients eligible for PE prompted the assessment of pre-operative predictors of 30-day major surgical complications.Methods
Demographics and surgical characteristics of patients undergoing PE for gynecologic cancer in a single institution between 01/2004–12/2016 were reviewed. Postoperative complications within 30?days following surgery were graded using the Accordion grading system. Logistic regression was used to analyze potential risk factors for severe postoperative complications.Results
A total of 138 patients were included in the cohort. Forty-five patients underwent total PE, 52 anterior PE, and 41 posterior PE. Among the 137 patients with follow-up, a severe postoperative complication was experienced by 37 patients (27.0%) and 3 patients (2.2%) experienced death within 90?days. The most frequent grade 3 complications were complications of urinary reconstruction (n?=?15), wound dehiscence (n?=?9), and abdominal abscess requiring intervention with drain or return to the operating room (n?=?6). On multivariable analysis, independent predictors of severe postoperative complications were anterior or total PE (adjusted odds ratio (aOR): 11.66, 95% CI 2.56–53.18), pre-operative hemoglobin ≤10?mg/dl (aOR 2.70, 95% CI 1.02–7.14) and presence of 3+ comorbidities (aOR: 2.76, 95% CI 1.07–7.10).Conclusions
Major complications after exenteration are common. Surgical complexity and patient selection play a considerable role in predicting complications. These data can be used to better risk stratify patients undergoing PE. 相似文献14.
Objective
Mesenchymal (MES) subtype of high-grade serous ovarian cancer (HGSOC) is associated with worse outcomes including survival and resectability compared with other molecular subtypes. Molecular subtypes have historically been derived from ‘tumor’, consisting of both cancer and stromal cells. We sought to determine the origins of multiple MES subtype gene signatures in HGSOC.Methods
Fifteen patients with MES subtype of HGSOC diagnosed between 2010 and 2013 were identified. Formalin-fixed paraffin-embedded (FFPE) blocks from primary surgery were sectioned for immunohistochemistry (IHC) staining of relevant proteins. Eight genes (ACTA2, COL5A1, COL11A1, FAP, POSTN, VCAN, ZEB1 and p-SMAD2) were selected for IHC staining based on their differential expression in MES vs. non-MES subtypes of HGSOC. Slides were scored for intensity and localization and simple statistics were used to compare expression results in cancer vs. stroma and between primary and metastatic sites.Results
COL5A1, VCAN, FAP, and ZEB1 proteins were almost exclusively expressed by stroma as opposed to cancer cells. In addition, stromal expression was dominant for ACTA2, COL11A1, POSTN and p-SMAD2. In general there were minimal differences in expression of proteins between primary and metastatic sites, exceptions being COL5A1 (reduced in metastases) and COL11A1 (increased in metastases). Nuclear p-SMAD2 expression was more common in metastatic stroma.Conclusions
The existing molecular classification of HGSOC MES subtype reflects a significant stromal contribution, suggesting an important role in HGSOC behavior and thus stroma may be a relevant therapeutic target. Specific patterns of expression indicate that collagens and TGF-β signaling are involved in the metastatic process. 相似文献15.
Erica M. Bednar Charlotte C. Sun Bethsaida Camacho John Terrell Alyssa G. Rieber Lois M. Ramondetta Ralph S. Freedman Karen H. Lu 《Gynecologic oncology》2019,152(2):328-333
Objective
The universal genetic testing initiative (UGTI) is a quality improvement effort to increase rates of guideline-based genetic counseling (GC) and genetic testing (GT) of patients with potentially hereditary cancers. The UGTI was disseminated to a county hospital gynecologic oncology clinic that serves a diverse, indigent patient population.Methods
Using the Model for Improvement quality improvement framework, interventions including integrated GC, clinic tracking, assisted GC referrals, and provider education were tested over 26?months. A retrospective data review included patients with high-grade, non-mucinous epithelial ovarian, fallopian tube, and primary peritoneal cancers (HGOC) and endometrial cancers (EC) diagnosed between 9/1/12–8/31/16. Statistical analyses were performed to describe the population and to evaluate rates of recommendation and use of immunohistochemistry tumor testing (IHC), GC, and GT.Results
A cohort of 241 patients (57 HGOC, 184 EC) were included. At the conclusion of the study 84.2% of HGOC patients were referred for GC, 89.6% (43/48) completed GC, and 90.7% (39/43) completed GT. Of EC patients, 81.0% were recommended to have IHC and 62.4% (93/149) completed IHC. Patients with HGOC diagnosed during dissemination of UGTI were significantly more likely to receive a recommendation for GC (p?=?0.02) and to complete GT (p?=?0.03) than those diagnosed before UGTI. Patients with EC were significantly more likely to complete IHC if diagnosed after UGTI than those diagnosed prior to dissemination (p?<?0.001).Conclusions
The UGTI can be adapted to increase use of guideline-based cancer genetics services in a diverse, indigent, gynecologic cancer patient population. 相似文献16.
Jung-Yun Lee Jeong-Yeol Park Sang Yoon Park Jeong-Won Lee Jae Weon Kim Yong Beom Kim Dae Hoon Jeong Kwang-Beom Lee Tae-Hun Kim In Ho Lee Min Chul Choi Ki Hyung Kim Yong-Man Kim Yong Jae Lee Sokbom Kang Eric Pujade-Lauraine 《Gynecologic oncology》2019,152(1):61-67
Purpose
To evaluate the effectiveness of bevacizumab with single-agent chemotherapy for platinum-resistant ovarian cancer in a real-world setting.Patients and methods
We enrolled recurrent platinum-resistant ovarian cancer patients from 27 institutions. All had received bevacizumab with single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin (PLD), topotecan) between 2015 and 2017 for second- or third-line chemotherapy in routine clinical practice. The primary endpoint was progression-free survival (PFS) and safety. Secondary endpoints included the objective response rate (ORR), PFS2, overall survival, duration of chemotherapy, and reasons for discontinuing chemotherapy.Results
Of 391 patients, 259 (66.2%) received bevacizumab with PLD, 94 (24.0%) with topotecan, and 38 (9.7%) with weekly paclitaxel. The median PFS was 6.1?months with all forms of bevacizumab-containing therapy. Although the cohort with weekly paclitaxel had a better PFS than the PLD cohort (P?=?0.028), this finding was not found in patients with a previous platinum-free interval of less than three months. The median duration of therapy was five cycles (range, one to 20?cycles), and 29 patients (7.4%) discontinued treatment because of adverse events from bevacizumab-containing regimens. The PLD cohort had fewer grade?≥?3 adverse events than the other regimens (PLD, 35.8%; weekly paclitaxel, 52.6%; topotecan, 51.1%; P?=?0.012), especially events of hematologic toxicities.Conclusion
In Korean ovarian cancer patients, the safety and effectiveness of chemotherapy with bevacizumab in a real-world setting was consistent with the results from a randomized controlled study. The effectiveness and toxicity profiles varied among the chemotherapy regimens, and this finding should be considered in practice.Clinical trials registration: NCT03367182. 相似文献17.
Chao-Chih Wu Chia-Sui Weng Yun-Ting Hsu Chih-Long Chang 《Taiwanese journal of obstetrics & gynecology》2019,58(1):145-152
Objective
Tyrosine-protein kinase MET (c-MET) has been reported to be a prognostic marker and suitable therapeutic target for ovarian cancer. BMS-777607, a small molecule, can inhibit MET and other protein kinase activities. The present study was conducted to investigate the mechanism of action and antitumor effect of BMS-777607 on ovarian cancer cells with constitutively activated c-MET.Materials and methods
Ovarian cancer cells with constitutively activated c-MET were first identified through Western blot analysis. Bio-behaviors, including signal transduction, proliferation, apoptosis, and migration, of the cells with constitutively activated c-MET were evaluated after BMS-777607 treatment. Liu's stain and immunological staining of α-tubuline were performed to evaluate the ploidy of the cells. A xenograft mouse model was also used to evaluate the antitumor effects of BMS-777607 on ovarian cancer cells with constitutively activated c-MET.Results
BMS-777607 could induce the highest inhibition of cell growth in ovarian cancer cells constitutively expressing c-MET. Treating SKOV3 cells with BMS-777607 could reduce c-MET activation and inhibit downstream cell signaling, thus causing cell apoptosis and polyploidy as well as cell cycle and cell migration inhibition. This molecule also inhibited tumor growth in a mouse xenograft model of SKOV3 ovarian cancer cells in vivo.Conclusion
BMS-777607 exhibits antitumor effects on ovarian cancer cells that constitutively express c-MET through c-MET signaling blockade and the inhibition of Aurora B activity. Combination treatments to enhance the effects of BMS-777607 warrant investigation in the future. 相似文献18.
Javaid Iqbal Alyssa Kahane Alison L. Park Tianhua Huang Wendy S. Meschino Joel G. Ray 《Journal d'obstetrique et gynecologie du Canada》2019,41(2):217-222
Objective
Some maternal hormone levels in pregnancy are associated with a higher risk of breast and ovarian cancer. This study systematically assessed the association between blood hormone levels measured in pregnancy and future risk of these cancers.Methods
Two reviewers independently conducted a literature search of MEDLINE and EMBASE databases from January 1970 to August 2017. Studies were included that measured one or more serum hormone levels in pregnancy and later assessed for cancer. Cancer outcomes were considered by cancer type, each in relation to a specific maternal hormone.Results
Eleven studies were included, comprising a total of 57 967 women. The interval between pregnancy and cancer onset varied from 4.1 to 20.5 years. Elevated serum chorionic gonadotropin (two of four studies) and alpha fetoprotein (two of three studies) were each associated with a lower risk of maternal breast cancer, whereas elevated estrone levels suggested a higher risk (one of three studies). Elevated testosterone (one of one study) and androstenedione (one of one study) were each associated with a significantly greater risk of sex-cord stromal ovarian tumours. Higher serum 17-hydroxyprogesterone was associated with an increased risk of sex-cord stromal (one of one study) and epithelial (one of one study) ovarian cancer.Conclusion
Observational studies suggest some degree of association between serum hormones measured in pregnancy and a woman's future risk of breast and ovarian cancer. More data are needed to determine sufficiently whether certain blood hormone levels measured in pregnancy are predictive of future cancer risk. 相似文献19.
C.E. Henry E. Llamosas B. Daniels A. Coopes K. Tang C.E. Ford 《Gynecologic oncology》2018,148(3):576-584
Objective
In recent years, the Wnt signalling pathway and the ROR1 and ROR2 receptors have been implicated in a range of gynecological cancers. These receptors have been described as prospective therapeutic targets, and this study investigated such potential in an endometrial cancer context.Method
Immunohistochemistry for ROR1 and ROR2 was performed in a patient cohort, and expression was correlated with clinicopathological parameters including type, stage, grade, myometrial invasion, lymphovascular involvement, patient age and survival. The functional role of these receptors in endometrial cancer was investigated via siRNA knockdown of ROR1 and ROR2 in three cell line models (KLE, RL95-2 and MFE-319). Effects on proliferation, adhesion, migration and invasion were measured.Results
High ROR1 expression in patient samples correlated with worse overall survival (p?=?0.0169) while high ROR2 expression correlated with better overall survival (p?=?0.06). ROR1 knockdown in KLE cells significantly decreased proliferation (p?=?0.047) and reduced migration and invasion. ROR2 knockdown in RL95-2 cells increased cell migration and invasion (p?=?0.011). Double ROR1 and ROR2 knockdown in MFE-319 cells decreased adhesion and significantly increased cell migration (P?=?0.008) and invasion (p?<?0.001).Conclusion
ROR1 and ROR2 play distinct roles in endometrial cancer. ROR1 may promote tumor progression, similar to its role in ovarian cancer, while ROR2 may act as a tumor suppressor in endometrioid endometrial cancer, similar to its role in colorectal cancer. With several ROR-targeting therapies currently in development and phase I clinical trials for other tumor types, this study supports the potential of these receptors as therapeutic targets for women with endometrial cancer. 相似文献20.
Mackenzie W. Sullivan Fabian T. Camacho Anne M. Mills Susan C. Modesitt 《Gynecologic oncology》2019,152(1):119-126