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1.
Gennaro Daniele Domenica Lorusso Giovanni Scambia Sabrina C. Cecere Maria Ornella Nicoletto Enrico Breda Nicoletta Colombo Grazia Artioli Lucia Cannella Giovanni Lo Re Francesco Raspagliesi Giuseppa Maltese Vanda Salutari Gabriella Ferrandina Stefano Greggi Alessandra Baldoni Alice Bergamini Maria Carmela Piccirillo Sandro Pignata 《Gynecologic oncology》2017,144(2):256-259
Background
Few data are available on the outcome of surgery after a bevacizumab-containing regimen. The MITO 16A- MaNGO OV2A phase 4 trial evaluates the outcomes of first-line CPB in a clinical-practice-like setting. Here we present the results of the subgroup of patients undergoing IDS after neoadjuvant treatment or suboptimal primary surgery.Methods
400 chemonaïve epithelial ovarian cancer patients, age ≥ 18, ECOG PS 0–2 were eligible to receive C (AUC 5 d1, q21) plus P (175 mg/m2 d1, q21) and B (15 mg/kg d1 q21) for 6 cycles followed by B maintenance until cycle 22nd.Results
79 patients (20%) underwent IDS. Overall, 74 patients received at least one administration of B before IDS. Median age was 61.2, 70% of the patients had FIGO IIIC disease. The median number of cycles before IDS was 3 both for chemotherapy and bevacizumab respectively. A residual disease ≤ 1 cm was achieved in 64 patients (86.5%). Four percent of the patients experienced fever and 4% required blood transfusion after surgery. Surgical wound infection and/or dehiscence, pelvic abscess, intestinal sub-occlusion and fistula were experienced by one patient each.Conclusions
In the MITO16A-MaNGO OV2A phase 4 trial, combined chemotherapy and bevacizumab did not hamper IDS and the rate of perioperative complications was similar to what expected without bevacizumab. These data support the hypothesis that adding bevacizumab to first line chemotherapy for ovarian cancer might not be denied to patients for whom IDS is planned. 相似文献2.
Boris J. Winterhoff Makayla Maile Amit Kumar Mitra Attila Sebe Martina Bazzaro Melissa A. Geller Juan E. Abrahante Molly Klein Raffaele Hellweg Sally A. Mullany Kenneth Beckman Jerry Daniel Timothy K. Starr 《Gynecologic oncology》2017,144(3):598-606
Objectives
The purpose of this study was to determine the level of heterogeneity in high grade serous ovarian cancer (HGSOC) by analyzing RNA expression in single epithelial and cancer associated stromal cells. In addition, we explored the possibility of identifying subgroups based on pathway activation and pre-defined signatures from cancer stem cells and chemo-resistant cells.Methods
A fresh, HGSOC tumor specimen derived from ovary was enzymatically digested and depleted of immune infiltrating cells. RNA sequencing was performed on 92 single cells and 66 of these single cell datasets passed quality control checks. Sequences were analyzed using multiple bioinformatics tools, including clustering, principle components analysis, and geneset enrichment analysis to identify subgroups and activated pathways. Immunohistochemistry for ovarian cancer, stem cell and stromal markers was performed on adjacent tumor sections.Results
Analysis of the gene expression patterns identified two major subsets of cells characterized by epithelial and stromal gene expression patterns. The epithelial group was characterized by proliferative genes including genes associated with oxidative phosphorylation and MYC activity, while the stromal group was characterized by increased expression of extracellular matrix (ECM) genes and genes associated with epithelial-to-mesenchymal transition (EMT). Neither group expressed a signature correlating with published chemo-resistant gene signatures, but many cells, predominantly in the stromal subgroup, expressed markers associated with cancer stem cells.Conclusions
Single cell sequencing provides a means of identifying subpopulations of cancer cells within a single patient. Single cell sequence analysis may prove to be critical for understanding the etiology, progression and drug resistance in ovarian cancer. 相似文献3.
Objective
Lynch syndrome (LS) is an inherited tumor predisposition condition caused by mutations in the mismatch repair (MMR) genes. Mutation carriers are at increased risk of various malignancies, including ovarian cancer (OC). Relatively little is known about the pathological features and clinical behavior of LS associated OC.Methods
We analyzed the data of 1047 proven MMR mutated individuals from a prospectively maintained database at a large referral center for genomic medicine in the North West of England. Data were crosschecked with pathology reports, the National Cancer Registry and death certificates, where appropriate. Data from gynecological surveillance and risk reducing surgery were analyzed.Results
We identified 53 cases of LSAOC in proven MMR mutated individuals. The cumulative risk of LSAOC was 20% at age 80 in those who retained their ovaries. LSAOC presented at an earlier age (average 51, range 24–70 years) than sporadic OC. The predominant histological subtype was endometrioid adenocarcinoma (53%). Most cases presented early (85% at stage I/II vs. 15% at stage III/IV, p < 0.001) and overall survival was excellent (80% 5-year survival), however, patients with advanced disease had a poor prognosis (40% 5-year survival). Most women were found to have LS after their OC diagnosis, however, two were detected at Stage 1c through gynecological surveillance and a further three were detected following surgery for screen-detected synchronous endometrial pathology.Conclusion
The predominance of early stage disease in LSAOC is linked to its good prognosis. We support risk-reducing surgery for women whose families are complete especially if undertaking hysterectomy for endometrial risk, and ovarian surveillance as part of gynecological screening for those who have not. 相似文献4.
Rachel Louise O&#x;Donnell Leen Verleye Nithya Ratnavelu Khadra Galaal Ann Fisher Raj Naik 《Gynecologic oncology》2017,144(2):438-447
Introduction
Treatment of locally advanced vulva cancer (LAVC) remains challenging. Due to the lack of randomised trials many questions regarding the indications for different treatment options and their efficacy remain unanswered.Methods
In this retrospective study we provide the largest published series of LAVC patients treated with anovulvectomy, reporting oncological outcomes and morbidity. Additionally, a systematic literature review was performed for all treatment options 1946–2015.Results
In our case series, 57/70 (81%) patients were treated in the primary setting with anovulvectomy and 13 patients underwent anovulvectomy for recurrent disease. The median overall survival (OS) was 69 months (1–336) with disease specific survival of 159 months (1–336). Following anovulvectomy for primary disease, time to progression and OS were significantly higher in node negative disease (10 vs. 96 months; 19 vs. 121 months, p < 0.0001). Post-surgical complications were observed in 36 (51.4%), the majority of which were Grade I/II infections. There was one peri-operative death.Review of the literature showed that chemotherapy, radiotherapy or combination treatments are alternatives to surgery. Evidence relating to all of these consisted mostly of small retrospective series, which varied considerably in terms of patient characteristics and treatment schedules. Significant patient and treatment heterogeneity prevented meta-analysis with significant biases in these studies. It was unclear if survival or morbidity was better in any one group with a lack of data reporting complications, quality of life, and long term follow-up. However, results for chemoradiation are encouraging enough to warrant further investigation.Conclusions
There remains inadequate evidence to identify an optimal treatment for LAVC. However, there is sufficient evidence to support a trial of anovulvectomy versus chemoradiation. Discussions and consensus would be needed to determine trial criteria including the primary outcome measure. Neoadjuvant chemotherapy or radiotherapy alone may be best reserved for the palliative setting or metastatic disease. 相似文献5.
Michelle van der Linden Melinda Schuurman Johan Bulten Maaike van der Aa Leon Massuger Joanne de Hullu 《Gynecologic oncology》2017,144(3):553-557
Aim
There is limited knowledge in the field of glandular vulvar malignancies. The aim of this study is to describe the incidence and survival of women with glandular vulvar malignancies.Methods
We searched PALGA, a nation-wide database registering all histo- and cytopathology in the Netherlands, for all cases of glandular vulvar malignancies between 2000 and 2015. Additional data were retrieved via the Netherlands Cancer Registry. Incidence rates were calculated per 1,000,000 women per year. Five-year net survival rates were calculated.Results
We identified 197 patients with a glandular vulvar malignancy. Of these patients 55% had a primary malignancy while 45% had secondary malignancies: expansion of another tumour in 17% and metastases or recurrences of another malignancy in 28%. There is a great variety of different diagnoses of primary vulvar malignancies: 11 different types were identified. We found an overall incidence rate of glandular vulvar malignancies of 0.9–2.5 per 1,000,000 women per year. Five-year net survival for patients with a primary malignancy was 68.5%. Most of the secondary vulvar malignancies originated from (ano-)rectal malignancies.Conclusion
Glandular vulvar malignancies are extremely rare and primary tumours are slightly more common. Overall survival of patients with primary glandular vulvar malignancies is comparable to patients with a vulvar squamous cell carcinoma, with five-year survival around 70%. The great variety in diagnoses combined with the low incidence should lead to routine pathologic revision and treatment in specialised gynaecologic oncology centres. 相似文献6.
Waqar Haque Vivek Verma Mohamad Fakhreddine Sandra Hatch E. Brian Butler Bin S. Teh 《Gynecologic oncology》2017,144(1):28-33
Purpose
The standard treatment for stage IB1 and IIA1 cervical carcinoma is surgery. For non-operative cases, the National Comprehensive Cancer Network recommends definitive radiotherapy (RT) with or without chemotherapy. This study sought to determine whether the addition of chemotherapy to RT improved overall survival (OS) for patients with stage IB1 and IIA1 cervical cancer.Methods
We used the National Cancer Data Base to identify patients with stage IB1 or stage IIA1 cervical cancer diagnosed in 2004 to 2012 who received definitive RT with or without chemotherapy. Patient, tumor, and treatment facility characteristics were assessed. Kaplan-Meier analysis was performed to compare overall survival (OS) between groups. Cox regression analysis was performed to identify factors associated with survival. Propensity-score matching was used to compare survival outcomes while accounting for indication bias.Results
825 patients met the specified criteria. 275 (33.3%) of patients received treatment with RT alone, whereas 550 (66.7%) were treated with CRT. The median OS in patients treated with RT alone was 121.1 months, while the median OS for patients treated with CRT was not reached (hazard ratio [HR] = 0.719; 95% confidence interval [CI] 0.549–0.945). Propensity-score matched analysis confirmed that CRT was superior to RT alone (HR = 0.701; 95% CI 0.509 to 0.963).Conclusions
Our study suggests the addition of chemotherapy to definitive RT in patients with stage IB1 or stage IIA1 cervical cancer is associated with an improvement in OS. Prospective studies are recommended to validate these results and to further investigate the quality of life differences associated with chemotherapy use. 相似文献7.
Stefania Bellone Eliana Bignotti Silvia Lonardi Francesca Ferrari Floriana Centritto Alice Masserdotti Francesca Pettinella Jonathan Black Gulden Menderes Gary Altwerger Pei Hui Salvatore Lopez Christopher de Haydu Elena Bonazzoli Federica Predolini Luca Zammataro Emiliano Cocco Federico Ferrari Alessandro D. Santin 《Gynecologic oncology》2017,144(1):146-152
Objective
Up to 12% of all endometrial-carcinomas (EC) harbor DNA-polymerase-ε-(POLE) mutations. It is currently unknown whether the favorable prognosis of POLE-mutated EC is derived from their low metastatic capability, extraordinary number of somatic mutations thus imparting immunogenicity, or a high sensitivity to chemotherapy.Methods
Polymerase-chain-reaction-amplification and Sanger-sequencing were used to test for POLE exonuclease-domain-mutations (exons 9–14) 131 EC. Infiltration of CD4 + and CD8 + T-lymphocytes (TIL) and PD-1-expression in POLE-mutated vs POLE wild-type EC was studied by immunohistochemistry (IHC) and the correlations between survival and molecular features were investigated. Finally, primary POLE-mutated and POLE-wild-type EC cell lines were established and compared in-vitro for their sensitivity to chemotherapy.Results
Eleven POLE-mutated EC (8.5%) were identified. POLE-mutated tumors were associated with improved progression-free-survival (P < 0.05) and displayed increased numbers of CD4 + (44.5 vs 21.8; P = 0.001) and CD8 + (32.8 vs 13.5; P < 0.001) TILs when compared to wild-type POLE EC. PD-1 receptor was overexpressed in TILs from POLE-mutated vs wild-type-tumors (81% vs 28%; P < 0.001). Primary POLE tumor cell lines were significantly more resistant to platinum-chemotherapy in-vitro when compared to POLE-wild-type tumors (P < 0.004).Conclusions
POLE ultra-mutated EC are heavily infiltrated with CD4 +/CD8 + TIL, overexpress PD-1 immune-check-point (i.e., features consistent with chronic antigen-exposure), and have a better prognosis when compared to other molecular subtypes of EC patients. POLE-mutated tumor-cell lines are resistant to platinum-chemotherapy in-vitro suggesting that the better prognosis of POLE-patients is not secondary to a higher sensitivity to chemotherapy but likely linked to enhanced immunogenicity. 相似文献8.
Carolyn K. McCourt Wei Deng Don S. Dizon Heather A. Lankes Michael J. Birrer Michele M. Lomme Matthew A. Powell James E. Kendrick Joel N. Saltzman David Warshal Meaghan E. Tenney David M. Kushner Carol Aghajanian 《Gynecologic oncology》2017,144(1):101-106
Background
The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS.Methods
Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40 mg/m2 as a 3 hour IV infusion on day 1 of a 21 day cycle. Treatment was continued until disease progression or unacceptable toxicity occurred.Results
Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68 years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2–25.1%); all were partial responses. Stable disease for at least 8 weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7 mo and 7.7 mo, respectively, with a median follow-up of 37 mo. Six month PFS was 20.6%. Major grade ≥ 3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS.Conclusion
In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity. 相似文献9.
Sofiane Bendifallah Lobna Ouldamer Vincent Lavoue Geoffroy Canlorbe Emilie Raimond Charles Coutant Olivier Graesslin Cyril Touboul Pierre Collinet Emile Daraï Marcos Ballester 《Gynecologic oncology》2017,144(1):107-112
Objectives
The purpose of this study was to analyse the endometrial cancer (EC) patterns of recurrence based on a large French multicentre database according to ESMO-ESGO-ESTRO classification.Methods
Data of women with histologically proven EC who received primary surgical treatment between January 2001 and December 2012 were retrospectively abstracted from seven institutions with prospectively maintained databases. The endpoints were recurrence, recurrence free survival (RFS) and overall survival (OS). Time to the first EC recurrence in a specific site was evaluated by using cumulative incidence analysis (Gray's test).Results
Data from 829 women were analysed in whom recurrences were observed in 176 (21%) with a median and mean time to recurrence of 13 and 19.5 months, respectively. High (35%) and high-intermediate risk groups (16%) were associated with higher recurrence rates compared with low (9%) and intermediate (9%) risk patients (p < 0.0001). Women with high risk EC had a higher 5-year cumulative incidence of distant recurrence (20.7%) than women with high-intermediate, intermediate and low risk EC (5.6%, 3.5%, 3.3%), (p < 0.001), respectively. Women with high risk and high-intermediate risk EC had a higher 5-year cumulative incidence of loco-regional recurrence (24.3% and 16.6%, respectively) than women with intermediate and low risk EC (6.6% and 6.5%, respectively), (p < 0.001).Conclusions
We report specific time and site patterns of first recurrence according to the ESMO/ESGO/ESTRO classification. Sites and hazard rates for recurrence differ widely between subgroups over time. Defining patterns of EC recurrence may provide useful information for developing follow-up recommendations and designing therapeutic approaches. 相似文献10.
Charlotte Gerd Hannibal Russell Vang Jette Junge Kirsten Frederiksen Robert J. Kurman Susanne K. Kjaer 《Gynecologic oncology》2017,144(1):174-180
Objective
Absolute risk and risk factors for recurrence and ovarian serous carcinoma following ovarian serous borderline tumors (SBTs) is not well-established.Methods
We included all women with SBTs in Denmark, 1978–2002. Diagnoses were confirmed by centralized pathology review and classified as atypical proliferative serous tumor (APST) or noninvasive low-grade serous carcinoma (LGSC). Implants were classified as noninvasive or invasive. Medical records were collected and reviewed, and follow-up was obtained. Subsequent diagnoses were also confirmed by centralized pathology review. We examined absolute risk and risk factors for recurrent APST and serous carcinoma using Cox regression.Results
The absolute serous carcinoma risk after, respectively, 5 and 20 years was 5.0% and 13.9% for noninvasive LGSC, and 0.9% and 3.7% for APST. Serous carcinoma risk was significantly higher following noninvasive LGSC compared with APST among stage I patients/patients without implants (HR = 5.3; 95% CI: 1.7–16.3), whereas no significant association with tumor type was found in advanced stage patients/patients with implants. Advanced stage – notably invasive implants – bilaterality, surface involvement, and residual disease increased serous carcinoma risk. However, women with stage I APST also had a higher risk than the general population.Conclusions
This largest population-based cohort of verified SBTs revealed that women with noninvasive LGSC are significantly more likely to develop serous carcinoma than women with APST, which could not entirely be explained by invasive implants. Although invasive implants was a strong risk factor for serous carcinoma, even women with stage I APST were at increased risk compared with the general population. 相似文献11.
Aoshuang Cheng Minghao Li Margaux J Kanis Ying Xu Qing Zhang Baoxia Cui Jie Jiang YouZhong Zhang Xingsheng Yang Beihua Kong 《Gynecologic oncology》2017,144(1):215-222
Objectives
To evaluate whether routine appendectomy is necessary in all patients with mucinous borderline ovarian tumor (mBOT) or mucinous ovarian cancer (MOC) who undergo gynecologic surgery.Methods
The database of Qilu Hospital was searched for women who underwent appendectomy in a primary surgery for an ovarian tumor between June 2005 and June 2015 and whose final diagnosis was mBOT, MOC or primary appendiceal tumor. A retrospective review was performed, as well as a meta-analysis of the literature to further validate the findings.Results
Seventy-one patients, 29 with mBOT and 42 with malignant mucinous tumors (including 40 with primary MOC and 2 with appendiceal mucinous adenocarcinoma), underwent appendectomy at the time of primary surgery. Among those with mBOT, two (6.9%) appendices were grossly abnormal and pathologically diagnosed with appendiceal implantation by mBOT. In the 42 patients with malignant disease, five (12%) appendices had a grossly abnormal appearance, one (2.4%) was diagnosed with an appendiceal metastasis from MOC and two (4.7%) were primary appendiceal adenocarcinoma. For grossly normal appendices, only one (2.4%) was confirmed to have microscopic metastasis from MOC.The meta-analysis included a total of 914 mBOT and MOC cases with appendectomies, including our current cases. The estimated rate of overall appendiceal pathology is 4.97%, and the pooled odds ratio (OR) showed statistical differences between MOC and mBOT (MOC vs. mBOT, OR = 2.15, P < 0.05). The estimated malignant pathology rate in macroscopically normal vs. abnormal appendices is 1.4% and 59%, respectively, with an estimated OR up to 97.5 (95% CI 28.1–338.5, P < 0.05).Conclusion
There is not sufficient evidence to support a routine appendectomy for patients with a grossly normal appendix in mBOT and MOC. A careful intra-operative exploration of the appendix is crucial, but appendectomy is only warranted when the appendix is abnormal. 相似文献12.
W. Ross Green Lara Hathout Atif J Khan Mohamed A Elshaikh Sushil Beriwal William Small Omar Mahmoud 《Gynecologic oncology》2017,144(2):299-304
Background
The primary treatment of early stage cervical carcinoma (IB-IIA) is either surgery or radiation therapy based on the pivotal Milan randomized study published twenty years ago. In the presence of high-risk features, the gold standard treatment is concurrent chemotherapy and radiation therapy (CRT) whether it is the in the postoperative or the definitive setting. Using the National Cancer Data Base (NCDB), the goal of our study is to compare the outcomes of surgery and radiation therapy in the chemotherapy era.Methods
Between 2004 and 2013, 5478 patients diagnosed with early stage cervical cancer were divided into 2 groups based on their primary treatment: non-surgical (n = 1980) and surgical groups (n = 3498). The distribution of patient/tumor characteristics and treatment variables with their relation to overall survival and proportional regression models were assessed to investigate the superiority of one approach over the other. Propensity score analysis adjusted for imbalance of covariates to create a well-matched-patient cohort.Findings
At 46 months median follow-up, the 5-year overall survival was similar between both groups (73·8% vs. 75.7%; p = 0.619) after applying propensity score analysis. On multivariate analysis, high Charlson comorbidity score, stage IIA disease, larger tumor size, positive lymph nodes and high-grade disease were significant predictors of poor outcome while older age and treatment approach were not.Interpretation
Our analysis suggests that surgery (followed by adjuvant RT or CRT) and definitive radiotherapy (with or without chemotherapy) result in equivalent survival. Prospective studies are warranted to establish this paradigm in the chemotherapy era. 相似文献13.
Lucas Gomes Sapienza Maria José Leite Gomes Vinicius Fernando Calsavara Mario M. Leitao Glauco Baiocchi 《Gynecologic oncology》2017,144(2):312-317
Purpose
To evaluate the impact of the extension of the radiotherapy field cranially toward para-aortic lymph nodes (EF-RT) in advanced cervical cancer.Materials and methods
A systematic search of databases (PubMed, CENTRAL, Clinical Trials) was performed and included studies that were published between 1960 and November 2015 without language restrictions. All randomized clinical trials (RCTs) were analyzed further. All patients must have undergone pelvic radiotherapy and the same systemic therapy in both arms. The primary endpoints were locoregional failure, incidence of distant metastasis, para-aortic failure, and cancer related death. The Mantel-Haenszel method was used in the meta-analysis. The risk of bias analysis was determined using the 7-domain method per the Cochrane Handbook for Systematic Reviews of Interventions V5.1.0. A review of the treatment technique and toxicity was also performed.Results
A total of 1309 studies were evaluated, 4 RCTs of which met the inclusion criteria; 506 patients were allocated to standard pelvic irradiation, and 494 underwent EF-RT. The risk of bias was considered to be low in nearly 80% of the domains. EF-RT significantly reduced the rate of para-aortic failure (HR 0.35, 95% CI 0.19–0.64; p < 0.01) and the incidence of other distant metastases (HR 0.69, 95% CI 0.50–0.96; p = 0.03). Locoregional failure and cancer-related death were not significantly altered (OR 1.06 [0.80–1.42]; p = 0.67, and 0.68 [0.45–1.01]; p = 0.06, respectively). The radiotherapy technique was conventional in 3 studies and conformational in 1 study. In total, 10 treatment-related deaths occurred—4 in pelvic radiation and 6 in EF-RT (OR 2.12 [0.71–6.27]; p = 0.18).Conclusions
EF-RT that targets the para-aortic lymphatic chain reduces distant metastatic events, but its impact on survival is unknown. Future studies should examine the value of EF-RT using modern radiation techniques. 相似文献14.
Roy Kessous Ido Laskov Jeremie Abitbol Joanna Bitharas Amber Yasmeen Shannon Salvador Susie Lau Walter H. Gotlieb 《Gynecologic oncology》2017,144(3):474-479
Objective
To evaluate clinical outcome in patients selected to receive neoadjuvant chemotherapy (NACT) compared to primary debulking surgery (PDS).Methods
Retrospective study including all consecutive patients diagnosed and treated for advanced (stages III-IV) ovarian cancers between the years 2003–2015.Results
263 women were included in the study, of these, 127 patients were selected to receive NACT and 136 were treated with PDS followed by adjuvant chemotherapy.PDS was associated with longer OS in stage IIIc disease (median OS: 60.2 vs. 48.8 months; p-value 0.039) compared with NACT.Patients achieved higher rates of complete cytoreduction in the NACT group compared to the PDS group (65.9% vs. 40.2%; p = 0.001). Patients attaining complete cytoreduction after PDS had the best survival, (median OS 106 months) followed by those with complete cytoreduction after NACT (median OS 71 months), followed by those with residual disease after PDS (median OS 55 months). Patients with residual disease following interval debulking after NACT had the worst outcome (median OS 36 months).Platinum sensitivity following first line and second line chemotherapy was similar whether patients received neoadjuvant chemotherapy or not.Conclusion
PDS was associated with improved outcome. NACT appears to improve survival outcome in patients that would have had residual disease after PDS, and attain complete cytoreduction at the time of interval cytoreduction. This treatment option can be used in selected patients that are not candidates for complete cytoreduction at PDS. 相似文献15.
Yoshiaki Maru Naotake Tanaka Miki Ohira Makiko Itami Yoshitaka Hippo Hiroki Nagase 《Gynecologic oncology》2017,144(2):377-383
Objective
Ovarian clear cell carcinoma (OCCC) is an aggressive ovarian cancer with a higher frequency in Japan and often becomes chemorefractory disease. Reliable genetic diagnosis is essential to affirm the success of precision medicine for OCCC treatment. The aim of this study is, therefore, to identify novel mutations in OCCCs and develop a feasible clinical next generation sequencing (NGS) approach using formalin-fixed paraffin-embedded (FFPE) rather than preferable but not always available fresh frozen (FF) samples.Methods
We optimized and evaluated exome analyses of 409 cancer-related genes using FFPE and FF DNA and analyzed NGS data to identify somatic mutations in Japanese OCCCs.Results
Sufficient and good quality DNAs from FFPE samples were extracted from 18 (FIGO Stage I: 12) out of 29 pairs of matched normal and OCCC for NGS (63%). The fine quality of extracted DNAs depended on the length of storage period (< 2 years storage). We also identified 45 somatic mutations in 34 genes including unreported variants from those FFPE DNA, in which somatic mutations in the PIK3CA gene was the most common (28%) as previously reported. Seven genes (PIK3CA, ARID1A, CTNNB1, CSMD3, LPHN3, LRP1B, and TP53) were mutated in at least two independent OCCCs. FF samples from 3 out of those 18 OCCCs were available and 13 out of 14 FFPE somatic mutations were confirmed.Conclusions
We successfully identified novel genetic alterations in Japanese OCCCs and demonstrated a feasible clinical diagnostic procedure using targeted NGS for OCCC FFPE samples. 相似文献16.
Objective
Health-related quality of life (HRQOL) has been found to be associated with overall survival in women with ovarian cancer. However, previous studies assessed HRQOL after surgery within clinical trial populations only. The study goal was to determine the association of pre-cancer diagnosis HRQOL with the likelihood of receiving surgery and with overall survival in a national, population-based cohort of older women with advanced ovarian cancer.Methods
The Surveillance, Epidemiology, and End Results (SEER)-Medicare Health Outcomes Survey (MHOS) database was queried to identify 374 women aged 65 years and older with advanced stage epithelial ovarian cancer from 1998 to 2011. Responses to the Short Form 36 (SF-36) and Veterans-RAND-12 (VR-12), two single-item global health questions, and Activities of Daily Living (ADLs) were abstracted. Multivariable models were used to quantify associations of HRQOL and ADL assessments with surgery and overall survival, adjusted for demographic and clinical characteristics.Results
Of 374 women with a HRQOL assessment prior to diagnosis, 199 (53%) underwent surgery. Increases in physical and mental HRQOL domains were significantly associated with receipt of surgery. The relationship between HRQOL domains and overall survival were not statistically significant. For ADLs, only difficulty in toilet use was significantly associated with survival.Conclusion
In this population-based sample of older women with advanced epithelial ovarian cancer, pre-diagnosis HRQOL was predictive of receiving surgery, but not of overall survival. 相似文献17.
Giovanni Damiano Aletti Annalisa Garbi Pietro Messori Maria Teresa Achilarre Vanna Zanagnolo Stefania Rizzo Sarah Alessi Luca Bocciolone Fabio Landoni Roberto Biffi Silvestro Carinelli Nicoletta Colombo Angelo Maggioni 《Gynecologic oncology》2017,144(3):468-473
Objective
The aim of the present study was to evaluate the impact of a multidisciplinary approach in patients' selection with advanced ovarian cancer (AOC) for different therapeutic strategies.Methods
Patients referred at our institution between 2009 and 2012 for AOC were included. Primary multidisciplinary evaluation was performed in all patients. Different strategies included: 1. patients referred to primary neoadjuvant chemotherapy (NACT) and interval surgery (IDS) (group A); 2. patients considered for surgical exploration. After surgical exploration, patients were either considered for primary debulking (PDS; group B), or NACT (group C).Results
A total of 363 patients were included. Of 38 patients (10.5%) in group A, 24 (63%) had sovradiaphragmatic/multiple liver metastases; 14 (37%) were excluded for PDS for anestehesiologic/medical reasons. Of 325 (89.5%) considered for surgical exploration, 295 (91%; group B) had primary surgery with debulking intent (N: 277) and were cytoreduced to no macroscopic disease (R0: N:200; 68%) o minimal RD < 5 mm (R1: N:77; 26%) or palliative intent (N:18; 6%); 30 (9%; group C) were referred for NACT. Of those, 27 (90%) underwent IDS, 3 had progressive disease. Overall survival (OS) and progression free survival (PFS) was different between the groups: OS: Group A: 34 months; Group B: 59 months; Group C: 29 months; p < 0.001. PFS: Group A: 10 months; Group B; 21 months; Group C: 12 months; p < 0.001.Conclusions
A multidisciplinary approach to patients referred to a tertiary center with AOC allows optimization of the treatment strategy, based on patients' characteristics (age, performance/nutritional status, comorbidities, functional status) and tumor diffusion (evaluated pre- and intraoperatively). 相似文献18.
Emma L. Kaderly Rasmussen Charlotte Gerd Hannibal Christian Dehlendorff Louise Baandrup Jette Junge Russell Vang Robert J. Kurman Susanne K. Kjaer 《Gynecologic oncology》2017,144(3):571-576
Objective
Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim.Methods
This nationwide case-control study included all women with an SBT diagnosis in Denmark, 1978–2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs).Results
We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p < 0.01). Older age at first birth also decreased the SBT risk (p = 0.03). An increased SBT risk was associated with infertility (OR = 3.31; 95% CI: 2.44–4.49), which was present both among parous and nulliparous women. HRT use increased the SBT risk (OR = 1.32; 95% CI: 1.02–1.72), whereas OC use decreased the risk (OR = 0.40; 95% CI: 0.26–0.62).Conclusions
Our nationwide study with expert histopathologic review of all SBTs showed that parity, infertility, use of HRT, and use of OCs, respectively, were strongly associated with the risk of SBTs. This is the first study to report a strong and significantly decreased SBT risk associated with OC use and a significantly increased risk with infertility, and HRT use. This supports that SBTs and serous ovarian cancer share similar risk factors. 相似文献19.
Jeffrey How Caroline Gauthier Jeremie Abitbol Susie Lau Shannon Salvador Raphael Gotlieb Manuela Pelmus Alex Ferenczy Stephan Probst Sonya Brin Asma Fatnassi Walter Gotlieb 《Gynecologic oncology》2017,144(3):503-509
Background
Sentinel lymph node (SLN) mapping has emerged as a promising solution to the ongoing debate regarding lymphadenectomy in the initial surgical management of endometrial cancer. Currently, little is known about its possible impact on location of disease recurrence compared to systematic lymphadenectomy.Methods
In this retrospective study, 472 consecutive patients with endometrial cancer who underwent either SLN mapping (SLN cohort, n = 275) or systematic lymphadenectomy (LND cohort, n = 197) from sequential, non-overlapping historical time points were compared. Clinical characteristics were extracted from a prospectively gathered electronic database. Both overall and pelvic sidewall recurrence free survival (RFS) were evaluated at 48-month post-operative follow-up.Results
No significant difference in overall RFS could be identified between the cohorts at 48 months (HR 0.74, 95% CI 0.43–1.28, p = 0.29). However, the SLN cohort had improved pelvic sidewall RFS compared to the LND cohort (HR 0.32, 95% CI 0.14–0.74, p = 0.007). The pelvic sidewall recurrences accounted for 30% of recurrences in the SLN cohort (8 out of 26 recurrences) compared to 71.4% in the LND cohort (20 out of 28 recurrences).Conclusions
SLN mapping may enable more efficient detection of the LNs at greatest risk of metastasis and help to guide adjuvant therapy, which in turn seems to decrease the risk of pelvic sidewall recurrences. 相似文献20.
Sarah E. Gill Michaela E. McGree Amy L. Weaver William A. Cliby Carrie L. Langstraat 《Gynecologic oncology》2017,144(2):266-273