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Background: Breast cancer 1, early onset ( BRCA1 ) is a tumour-suppressor gene associated with familial epithelial ovarian cancer (EOC). Reduced BRCA1 expression is associated with enhanced sensitivity to platinum-based chemotherapy. We sought to examine the prognostic relevance of BRCA1 expression in EOC patients treated with intraperitoneal platinum/taxane. Methods: The GOG-172 was a phase III, multi-institutional randomised trial of intravenous paclitaxel and cisplatin (IV therapy) vs intravenous paclitaxel, intraperitoneal cisplatin plus paclitaxel (IP therapy) in patients with optimally resected stage III EOC. The BRCA1 expression was assessed with immunohistochemistry (IHC) staining blinded to clinical outcome in archival tumour specimens. Slides with ⩽10% staining were defined as aberrant and >10% as normal. Correlations between BRCA1 expression and progression-free survival (PFS) and overall survival (OS) were analysed using Kaplan–Meier method and Cox regression analysis. Results: Of the 393 patients, 189 tumours had aberrant expression, and 204 had normal BRCA1 expression. There was an interaction between BRCA1 expression and route of administration on OS ( P =0.014) but not PFS ( P =0.054). In tumours with normal BRCA1 expression, the median OS was 58 months for IP group vs 50 months for IV group ( P =0.818). In tumours with aberrant BRCA1 expression, the median OS was 84 vs 47 months in the IP vs IV group, respectively ( P =0.0002). Aberrant BRCA1 expression was an independent prognostic factor for better survival in women randomised to IP therapy (hazard ratio (HR)=0.67, 95% confidence interval (CI)=0.47–0.97, P =0.032). Similar survival was observed in the IV and IP patients with normal BRCA1 expression. Multivariate but not univariate modelling demonstrated that IV patients with aberrant vs normal BRCA1 expression had worse survival. Conclusion: Decreased BRCA1 expression is associated with a 36-month survival improvement in patients with EOC treated with IP chemotherapy. Although these results merit validation in future studies, the results suggest that decreased BRCA1 expression predicts for improved response to cisplatin-based IP chemotherapy with cisplatin and paclitaxel.

Background The lymphadenectomy in the treatment of endometrial cancer is a topic of ongoing debate. The direct comparison between no lymphadenectomy, pelvic lymphadenectomy, and pelvic/para-aortic lymphadenectomy regarding overall survival of patients with endometrial cancer is missing. Methods We performed a multicenter, retrospective, registry-based study of 1502 patients with endometrial cancer treated with no lymphadenectomy ( n  = 697), systemic pelvic lymphadenectomy ( n  = 543) and systemic pelvic/para-aortic lymphadenectomy ( n  = 262). The patients were divided into three groups of recurrence risk: low, intermediate, and high. The outcome measure was overall survival. Results Median follow-up was 78 months. Lymphadenectomy did not improve overall survival of patients with low risk of recurrence. The survival effect of systemic lymphadenectomy was significant in patients with intermediate and high risk of recurrence. Multivariate analysis showed that both pelvic (HR 0.63, CI 0.38–0.82, p  = 0.001) and combination of pelvic/para-aortic lymphadenectomy (HR 0.50, CI 0.43–0.81, p  < 0.0001) significantly reduced the mortality risk in patients with intermediate risk compared to the patients who underwent no lymphadenectomy. In patients with high risk, only combined pelvic/para-aortic lymphadenectomy (HR 0.62, CI 0.48–0.82, p  = 0.005) was associated with decreased mortality rate compared with no lymphadenectomy. Among patients with intermediate and high risk of recurrence who did not receive any adjuvant therapy, pelvic/para-aortic lymphadenectomy significantly reduced the mortality risk (HR 0.52, CI 0.37–0.73, p  < 0.0001) in comparison with no lymphadenectomy. This management was superior to pelvic lymphadenectomy alone. In patients with low risk of recurrence, lymphadenectomy had no effect on overall survival. Conclusions Pelvic/para-aortic lymphadenectomy should be performed in all patients with endometrial cancer at intermediate and high risk of recurrence.

Background Little data exist about the clinical management and survival of elderly patients with endometrial cancer. This study aimed to evaluate the management of elderly and very elderly patients with endometrial cancer as well as the overall survival (OS) rate, disease-free survival (DFS) rate, and cancer-specific survival (CSS) rate in a multicenter cohort. Methods Data from 1228 patients with endometrial cancer who received primary treatment between January 2001 and December 2012 were collected from a multicenter database. Clinical management, DFS, CSS, and OS were analyzed. Results Based on the international endometrial cancer risk classification, 36% (212/582) of women age 65 years or younger, 42% (220/526) of women ages 65–80 years, and 48% (58/120) of women older than 80 years showed high-risk endometrial cancer ( p  < 0.001). Pelvic lymphadenectomy was performed for 85% (230/271) of the women age 65 years or younger and 46% (33/71) of the women older than 80 years ( p  < 0.001). Radiotherapy was performed for 27% (33/120) of the very elderly and 40% (233/582) of the young patients ( p  = 0.009). The 3-year CSS rates were 95% (95% confidence interval [CI], 93–97%) for the women age 65 years or younger, 90% (95% CI, 87–94%) for the women ages 65–80 years, and 82% (95% CI, 73–93%) for the women older than 80 years ( p  < 0.001). Conclusions The elderly and very elderly patients with endometrial cancer showed poorer prognosis than young patients. The significant lower CSS rate for the elderly patients could have be due to both the higher rate of high-risk endometrial cancer and undertreatment. Specific guidelines for the management of elderly and very elderly patients with endometrial cancer are needed to improve their prognosis.

To investigate the role of the lncRNA growth arrest special 5 (GAS5) in ovarian clear cell carcinoma (OCCC), we measured the expression of GAS5 and miR‐31‐5p in OCCC tissue samples and OCCC cell lines using RT‐qPCR. MTT and colony formation assays were used to measure cell viability and colony formation ability. Cell invasion was determined by Transwell assays. The binding between GAS5 and miR‐31‐5p as well as miR‐31‐5p and ARID1A was determined by dual‐luciferase reporter assays. The ARID1A protein levels were detected using western blotting. Kaplan–Meier curves were used for the analysis of the 5‐year survival rate of patients with OCCC. GAS5 and ARID1A levels were significantly decreased, while miR‐31‐5p levels were strongly elevated in the OCCC tissues and cell lines. Patients with lower GAS5/ARID1A levels had shorter overall survival times. Overexpression of GAS5 or inhibition of miR‐31‐5p suppressed cell viability and invasion of OCCC cells and upregulated the protein levels of ARID1A. Moreover, overexpression of miR‐31‐5p reversed the effects of overexpression of GAS5. Cotransfection with pcDNA3.1‐GAS5 and miR‐31‐5p inhibitor led to the lowest cell viability and cell invasion rates. A dual‐luciferase reporter assay was performed to confirm the target relationship between GAS5 and miR‐31‐5p, as well as between miR‐31‐5p and ARID1A. LncRNA GAS5 inhibited cell viability and invasion of OCCC through activation of ARID1A by sponging miR‐31‐5p.

Background Ovarian clear cell carcinoma (OCCC) is a rare histologic type of ovarian cancer. There is a lack of an efficient prognostic predictive tool for OCCC in clinical work. This study aimed to construct and validate nomograms for predicting the overall survival (OS) and cancer-specific survival (CSS) in patients with OCCC. Methods Data of patients with primary diagnosed OCCC in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016 was extracted. Prognostic factors were evaluated with LASSO Cox regression and multivariate Cox regression analysis, which were applied to construct nomograms. The performance of the nomogram models was assessed by the concordance index (C-index), calibration plots, decision curve analysis (DCA) and risk subgroup classification. The Kaplan-Meier curves were plotted to compare survival outcomes between subgroups. Results A total of 1541 patients from SEER registries were randomly divided into a training cohort ( n  = 1079) and a validation cohort ( n  = 462). Age, laterality, stage, lymph node (LN) dissected, organ metastasis and chemotherapy were independently and significantly associated with OS, while laterality, stage, LN dissected, organ metastasis and chemotherapy were independent risk factors for CSS. Nomograms were developed for the prediction of 3- and 5-year OS and CSS. The C-indexes for OS and CSS were 0.802[95% confidence interval (CI) 0.773–0.831] and 0.802 (0.769–0.835), respectively, in the training cohort, while 0.746 (0.691–0.801) and 0.770 (0.721–0.819), respectively, in the validation cohort. Calibration plots illustrated favorable consistency between the nomogram predicted and actual survival. C-index and DCA curves also indicated better performance of nomogram than the AJCC staging system. Significant differences were observed in the survival curves of different risk subgroups. Conclusions We have constructed predictive nomograms and a risk classification system to evaluate the OS and CSS of OCCC patients. They were validated to be of satisfactory predictive value, and could aid in future clinical practice.

Ovarian clear cell carcinoma (OCCC) is the second common histology of epithelial ovarian cancer in Taiwan. Stage IC is common, especially during minimally invasive surgery. Adjuvant chemotherapy in stage IC OCCC is unavoidable, and paclitaxel-based chemotherapy in Taiwan is self-paid. However, surgical spillage from minimally invasive surgery as a cause of unfavorable prognosis is still uncertain. The information of patients with stage IC OCCC, corresponding to a period of January 1995 to December 2016, was retrospectively collected following a chart and pathology review. Data regarding surgical methods, cytology status, regimens of adjuvant chemotherapy, survivorship, progression-free survival (PFS), and overall survival (OS) period were analyzed. In total, 88 patients were analyzed, and 64 and 24 patients were treated with paclitaxel- and nonpaclitaxel-based chemotherapy, respectively. Recurrence was identical between the two groups: PFS (47.5 ± 41.36 versus 54.0 ± 53.9 months, p = 0.157) and OS (53.5 ± 38.14 versus 79.0 ± 49.42 months, p = 0.070). Of the 88 patients, 12 had undergone laparoscopy for histological confirmation before complete open staging surgery; however, their PFS (49.5 ± 46.84 versus 49.0 ± 35.55 months, p = 0.719) and OS (56.5 ± 43.4 versus 51.0 ± 32.77 months, p = 0.600) were still comparable. Cytology results were only available for 51 patients, and positive washing cytology results seemed to worsen PFS (p = 0.026) but not OS (p = 0.446). In conclusion, adjuvant nonpaclitaxel chemotherapy and laparoscopic tumor spillage before the staging operation did not worsen the outcome in stage IC OCCC. Positive washing cytology has a negative effect on PFS but not on OS.

OBJECTIVENeoadjuvant chemotherapy (NACT) followed by surgery is a different therapeutic approach to locally advanced cervical adenocarcinoma (LACA) and seems to offer specific advantages over chemoradiation. This phase II trial was designed to evaluate the toxicity and activity of NACT with cisplatin-adriamycin-paclitaxel (TAP) in patients with LACA. METHODSPatients with International Federation of Gynecology and Obstetrics stage IB2–IIB uterine adenocarcinoma were treated with NACT TAP for 3 cycles. After the last cycle, patients underwent radical surgery with lymph node dissection. Pathological response was classified as no residual tumor (pCR), residual disease with less than 3-mm stromal invasion (pR1), or residual disease with more than 3-mm stromal invasion (pR2). RESULTSBetween 2003 and 2010, 30 women were enrolled. Fourteen complete clinical responses, 10 partial responses, and 6 stabilizations of disease were registered. Three patients achieved a pCR, 6 a pR1 response, and 21 a pR2 response. At a median follow-up of 45 months, progression-free survival and overall survival were 37 and 48 months, respectively. Hematologic toxicity was the most relevant adverse effect. CONCLUSIONSThe TAP combination seems to be feasible with an acceptable toxicity profile and a promising response rate for the treatment of LACA.

IntroductionThe standard treatment of ovarian cancer is the combination of debulking surgery and chemotherapy. There is an ongoing discussion on which treatment is best: primary debulking surgery (PDS) or neoadjuvant chemotherapy with interval debulking (NACT-IDS). Even a large randomized trial has not settled this issue. We examined whether comparing a specified treatment protocol would not be a more logical approach to answer this type of discussions.MethodsA retrospective study of 142 consecutively treated patients according to a fixed protocol between 2000 and 2012 was conducted. Disease-free survival and overall survival were calculated by univariate and multivariate analyses for the whole group and for advanced stages separately. Specific differences between PDS and NACT-IDS were studied. Comparison of results from large databases was made.ResultsDisease-free survival and overall 5-year survival for the whole group were 35% and 50%. For the advanced stages, disease-free survival and overall 5-year survival were 14% and 36%, with a median disease-free and overall survival of 16 and 44 months. Of the 98 women with advanced ovarian carcinoma, 54% of operable patients underwent PDS and 44% underwent NACT-IDS. More patients in the PDS group were optimally (<1 cm) debulked: 80% vs 71%. There was no significant difference in survival between PDS or NACT-IDS. Optimally debulked patients had a significant better overall survival in multivariate analysis with a hazard ratio of 2.1.DiscussionOutcome of treatment according to a fixed protocol with a mixture of PDS and NACT-IDS was similar to results from large databases. We hypothesize that comparison of a specific strategy may yield more useful results than awaiting the perfect randomized trial.

Objective: The prognosis for patients with platinum-resistant advanced ovarian cancer remains poor. The impact of approved agents on survival has not been clarified during the last decade. We studied survival trends during the last 15 years in platinum-resistant patients treated with cytoreductive surgery followed by paclitaxel/platinum chemotherapy. Methods: Patients with epithelial ovarian, fallopian or peritoneal cancer, stages III/IV and platinum-resistant disease after first-line chemotherapy with paclitaxel/platinum were included. They were grouped according to the period of chemotherapy: group A 31/3/1995–31/12/2001 (n = 56) and Group B 1/1/2002–24/12/2008 (n = 57). In order to compensate for the difference in follow-up between the 2 groups, we performed minimum follow-up (MFU) analyses by considering as cases only women who had an event within 3 years of follow-up. Patients with no events for up to 3 years were censored at that time. Results: MFU analyses showed that median overall survival (OS) was significantly longer in group B: 12.3 vs. 17.5 months (p = 0.012). This was due to a doubling of the median OS after relapse: 5.7 vs. 10.9 months (p = 0.0180). Multivariate Cox regression indicated group and histology as factors statistically significantly associated with OS. Following relapse, patients in group B were predominantly treated with liposomal doxorubicin and gemcitabine, and patients in group A were treated with platinum compounds, docetaxel and oral etoposide (p < 0.001). Conclusions: The introduction of novel agents without cross-resistance to platinum or taxanes has improved the prognosis of platinum-resistant patients.

Background: Dose-intensive chemotherapy with hematopoietic stem cell transplantation has been evaluated as a salvage treatment for recurrent ovarian cancer, but its benefit has not yet been demonstrated. In a previous phase I trial, we reported the feasibility of administering topotecan as a salvage regimen. Methods: Twenty-one patients were treated with escalating doses of topotecan associated with a fixed dose of cyclophosphamide. Results: The maximum tolerated dose was established at 9.0 mg/m2 on a 5-day regimen, analogously to what was reported for topotecan monotherapy. One toxic death from septic shock and multiorgan failure occurred. Although hematopoietic toxicities were overcome by peripheral blood stem cell transplantation, superior nonhematological toxicities were observed as compared to the initial trial. Conclusion: Response rates were generally short and survival rates were poor. Results of the ITOV 01bis study demonstrate that, in the setting of recurrent ovarian cancer, intensive chemotherapy based on topotecan-cyclophosphamide association is not currently clinically indicated.