Publications
243 results found
Ciavattini A, Carpini GD, Giannella L, et al., 2020, European Federation for Colposcopy (EFC) and European Society of Gynaecological Oncology (ESGO) joint considerations about human papillomavirus (HPV) vaccination, screening programs, colposcopy, and surgery during and after the COVID-19 pandemic, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 30, Pages: 1097-1100, ISSN: 1048-891X
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- Citations: 29
Heinonen A, Jakobsson M, Kiviharju M, et al., 2020, Role of Colposcopy after Treatment for Cervical Intraepithelial Neoplasia, CANCERS, Vol: 12
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- Citations: 3
Paraskevaidi M, Morais CLM, Ashton KM, et al., 2020, Detecting endometrial cancer by blood spectroscopy: a diagnostic cross-sectional study, Cancers, Vol: 12, Pages: 1-17, ISSN: 2072-6694
Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention.
Athanasiou A, Bowden S, Paraskevaidi M, et al., 2020, HPV vaccination and cancer prevention, Best Practice and Research: Clinical Obstetrics and Gynaecology, Vol: 65, Pages: 109-124, ISSN: 1521-6934
Prophylactic vaccines have been found to be highly effective in preventing infection and pre-invasive and invasive cervical, vulvovaginal and anal disease caused by the vaccine types. HPV vaccines contain virus-like particles that lack the viral genome and produce high titres of neutralising antibodies. Although the vaccines are highly effective in preventing infections, they do not enhance clearance of existing infections. Vaccination programmes target prepubertal girls and boys prior to sexual debut as efficacy is highest in HPV naïve individuals. School-based programmes achieve higher coverage, although implementation is country specific. Vaccination of older women may offer some protection and acceleration of impact, although this may not be cost-effective. HPV-based screening will continue for vaccinated cohorts, although intervals may increase.
Valasoulis G, Pouliakis A, Michail G, et al., 2020, Alterations of HPV-Related Biomarkers after Prophylactic HPV Vaccination. A Prospective Pilot Observational Study in Greek Women, CANCERS, Vol: 12
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- Citations: 19
Paraskevaidis E, Athanasiou A, Paraskevaidi M, et al., 2020, Cervical pathology following HPV vaccination in Greece: A 10-year HeCPA observational cohort study, In Vivo: international journal of experimental and clinical pathophysiology and drug research, Vol: 34, Pages: 1445-1449, ISSN: 0258-851X
Background: In Greece the population-level impact of HPV vaccination is unknown due to lacking official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy.Materials and Methods: This is an observational prospective cohort study performed in 7 academic Obstetrics & Gynaecology departments across Greece between 2009-2019. Cases were women that had completed HPV vaccination before coitarche and were referred for colposcopy due to abnormal cytology. For each vaccinated woman an unvaccinated matched control was selected. Results: A total of 849 women who had been vaccinated before coitarche and 849 unvaccinated controls were recruited. The combination of cytological, colposcopic and molecular findings necessitated treatment in only a single case among vaccinated (0.1%) and in 8.4% among unvaccinated. Conclusion: Despite potential bias, this study’s message is clear: HPV vaccination at a proper age can markedly reduce development of severe cervical precancer and consequently, the need for treatments with their long-term related obstetrical morbidity.
Mitra A, MacIntyre D, Ntritsos G, et al., 2020, The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions, Nature Communications, Vol: 11, Pages: 1-13, ISSN: 2041-1723
Emerging evidence suggests associations between the vaginal microbiota (VMB) composition, human papillomavirus (HPV) infection, and cervical intraepithelial neoplasia (CIN); however, causal inference remains uncertain. Here, we use bacterial DNA sequencing from serially collected vaginal samples from a cohort of 87 adolescent and young women aged 16–26 years with histologically confirmed, untreated CIN2 lesions to determine whether VMB composition affects rates of regression over 24 months. We show that women with a Lactobacillus-dominant microbiome at baseline are more likely to have regressive disease at 12 months. Lactobacillus spp. depletion and presence of specific anaerobic taxa including Megasphaera, Prevotella timonensis and Gardnerella vaginalis are associated with CIN2 persistence and slower regression. These findings suggest that VMB composition may be a future useful biomarker in predicting disease outcome and tailoring surveillance, whilst it may offer rational targets for the development of new prevention and treatment strategies.
J Bowden S, Kyrgiou M, 2020, Human papillomavirus, Obstetrics, Gynaecology & Reproductive Medicine, Vol: 30, Pages: 109-118, ISSN: 1751-7214
Human papillomaviruses are ancient small DNA viruses and represent the most common sexually transmitted infection in the world. In the majority, HPV infection is cleared by an incompletely understood immune response. HPV is a necessary but not sufficient cause of cervical cancer, and responsible for a proportion of other anogenital cancers including vulval, vaginal, anal and oropharyngeal. Oncogenesis is likely mediated through viral proteins which hijack host-cell machinery in epithelial keratinocytes and disrupt host tumour-suppressor proteins. Much work has been undertaken to further characterise the natural history of HPV infection and cervical disease. Such efforts have been translated to important public health interventions like the introduction of HPV tests in cervical screening. HPV vaccination programmes are expected to further reduce the incidence of high-risk HPV infections and resultantly HPV-related disease.
Raglan O, Assi N, Nautiyal J, et al., 2020, Proteomic analysis of malignant and benign endometrium according to obesity and insulin-resistance status using Reverse Phase Protein Array, Publisher: ELSEVIER SCIENCE INC, Pages: 57-72, ISSN: 1931-5244
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- Citations: 7
Tzafetas M, Mitra A, Paraskevaidi M, et al., 2020, The intelligent-Knife (i-Knife) and its intraoperative diagnostic advantage for the treatment of cervical disease, Proceedings of the National Academy of Sciences of USA, Vol: 117, Pages: 7338-7346, ISSN: 0027-8424
Clearance of surgical margins in cervical cancer prevents the need for adjuvant chemoradiation and allows fertility preservation. In this study, we determined the capacity of the rapid evaporative ionization mass spectrometry (REIMS), also known as intelligent knife (iKnife), to discriminate between healthy, preinvasive, and invasive cervical tissue. Cervical tissue samples were collected from women with healthy, human papilloma virus (HPV) ± cervical intraepithelial neoplasia (CIN), or cervical cancer. A handheld diathermy device generated surgical aerosol, which was transferred into a mass spectrometer for subsequent chemical analysis. Combination of principal component and linear discriminant analysis and least absolute shrinkage and selection operator was employed to study the spectral differences between groups. Significance of discriminatory m/z features was tested using univariate statistics and tandem MS performed to elucidate the structure of the significant peaks allowing separation of the two classes. We analyzed 87 samples (normal = 16, HPV ± CIN = 50, cancer = 21 patients). The iKnife discriminated with 100% accuracy normal (100%) vs. HPV ± CIN (100%) vs. cancer (100%) when compared to histology as the gold standard. When comparing normal vs. cancer samples, the accuracy was 100% with a sensitivity of 100% (95% CI 83.9 to 100) and specificity 100% (79.4 to 100). Univariate analysis revealed significant MS peaks in the cancer-to-normal separation belonging to various classes of complex lipids. The iKnife discriminates healthy from premalignant and invasive cervical lesions with high accuracy and can improve oncological outcomes and fertility preservation of women treated surgically for cervical cancer. Larger in vivo research cohorts are required to validate these findings.
Weston G, Dombrowski C, Harvey MJ, et al., 2020, Use of the Aptima mRNA high-risk human papillomavirus (HR-HPV) assay compared to a DNA HR-HPV assay in the English cervical screening programme: a decision tree model based economic evaluation, BMJ OPEN, Vol: 10, ISSN: 2044-6055
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- Citations: 13
Beaver K, Martin-Hirsch P, Williamson S, et al., 2020, Exploring the acceptability and feasibility of patient-initiated follow-up for women treated for stage I endometrial cancer, European Journal of Oncology Nursing (EJON), Vol: 44, ISSN: 1462-3889
PURPOSE: There is a strong shift away from hospital-based approaches to follow-up after active treatment for cancer with supported self-management being promoted as an approach to long term recovery. We aimed to determine the acceptability and feasibility of patient-initiated follow-up (PIFU), supported by a self-management approach, for patients treated for Stage I endometrial cancer. METHODS: A mixed methods study was undertaken. Participants were asked to forego hospital outpatient follow-up appointments, supported by a self-management approach. Outcome measures included satisfaction with information and service, psychological morbidity, quality of life and preferences for follow-up. Qualitative interviews were carried out with study participants to determine their views on follow-up in general and PIFU in particular. RESULTS: We recruited 17 patients. High levels of satisfaction were evident with no physical or psychological detriment. Self-management was a favoured option. Participants questioned the value of hospital follow-up and were willing to engage in self-management if they knew who to contact if they had a problem and were aware of the signs and symptoms of recurrence. However, uptake to the study was low and further work is needed to explore if recruitment to a randomised controlled trial (RCT) is a viable option. CONCLUSIONS: Alternative approaches to hospital-based follow-up need to demonstrate that patients feel supported, knowing what symptoms to report and to whom. This study shows acceptability of a supported self-management approach but raises some concerns about the feasibility of recruitment to a future RCT.
Kalliala I, Athanasiou A, Veroniki AA, et al., 2020, Incidence and mortality from cervical cancer and other malignancies after treatment of cervical intraepithelial neoplasia: a systematic review and meta-analysis of the literature., Annals of Oncology, Vol: 31, Pages: 213-227, ISSN: 0923-7534
Background: While local treatments for cervical intraepithelial neoplasia (CIN) are highly effective, it has been reported that treated women remain at increased risk of cervical and other cancers. Our aim is to explore the risk of developing or dying from cervical cancer and other HPV- and non-HPV-related malignancies after CIN treatment and infer about its magnitude compared to general population.Materials and methods:Design: Systematic review and meta-analysis.Eligibility criteria: Studies with registry-based follow-up reporting cancer incidence or mortality after CIN treatment. Data synthesis: Summary effects were estimated using random-effects models.Outcomes: Incidence rate of cervical cancer among women treated for CIN (per 100,000 woman-years). Relative risk (RR) of cervical cancer, other HPV-related anogenital tract cancer (vagina, vulva, anus), any cancer, and mortality, for women treated with CIN versus the general population.Results: Twenty-seven studies were eligible. The incidence rate for cervical cancer after CIN treatment was 39 per 100,000 woman-years (95% CI 22 to 69). RR of cervical cancer was elevated compared to the general population (3·30, 2·57 to 4·24; P<0·001). RR was higher for women over 50 years old and remained elevated for at least 20 years after treatment. RR of vaginal (10·84, 5·58 to 21·10; P<0·001), vulvar (3·34, 2·39 to 4·67; P<0·001), and anal cancer (5·11, 2·73 to 9·55; P<0·001) was also higher. Mortality from cervical/vaginal cancer was elevated, but our estimate was more uncertain (RR 5·04, 0·69 to 36·94; P=0·073).Conclusions: Women treated for CIN have considerably higher risk to be later diagnosed with cervical and other HPV-related cancers compared to general population. The higher risk of cervical cancer lasts for at least 20 years after treatment and is higher for women
Lathouras K, Saso S, Jones BP, et al., 2020, Transvaginal laparoscopic salpingo-oophorectomy: an oncological risk-reducing procedure, FUTURE SCIENCE OA, Vol: 6, ISSN: 2056-5623
Pargianas M, Salta S, Apostolopoulou K, et al., 2020, Pathways Involved in Premature Ovarian Failure: A Systematic Review of Experimental Studies, CURRENT PHARMACEUTICAL DESIGN, Vol: 26, Pages: 2087-2095, ISSN: 1381-6128
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- Citations: 3
Raglan O, Assi N, Nautiyal J, et al., 2019, Proteomic analysis of malignant and benign endometrium according to obesity and insulin resistance status using Reverse Phase Protein Array, Translational Research: the journal of laboratory and clinical medicine, ISSN: 0022-2143
Obesity and hyperinsulinemia are known risk factors for endometrial cancer, yet thebiological pathways underlying this relationship are incompletely understood. Thisstudy investigated protein expression in endometrial cancer and benign tissue andits correlation with obesity and insulin resistance.One hundred and seven women undergoing hysterectomy for endometrial canceror benign conditions provided a fasting blood sample and endometrial tissue. Weperformed proteomic expression according to body mass index, insulin resistance,and serum marker levels. We used linear regression and independentttest for statis-tical analysis. Proteomic data from 560 endometrial cancer cases from The CancerGenome Atlas (TCGA) databank were used to assess reproducibility of results.One hundred and twenty seven proteins were significantly differentially expressedbetween 66 cancer and 26 benign patients. Protein expression involved in cellcycle progression, impacting cytoskeletal dynamics (PAK1) and cell survival (Rab25), were most significantly altered. Obese women with cancer had increasedPRAS40_pT246; a downstream marker of increased PI3K-AKT signaling. Obesewomen without cancer had increased mitogenic and antiapoptotic signaling byway of upregulation of Mcl-1, DUSP4, and Insulin Receptor-b.This exploratory study identified a number of candidate proteins specific to endo-metrioid endometrial cancer and benign endometrial tissues. Obesity and insulinresistance in women with benign endometrium leads to specific upregulation ofproteins involved in insulin and driver oncogenic signaling pathways such as thePI3K-AKT-mTOR and growth factor signaling pathways which are mitogenic andalso disruptive to metabolism. (Translational Research 2020; 000:1 16)
Bowden SJ, Kalliala I, Veroniki AA, et al., 2019, The use of Human Papillomavirus DNA Methylation in cervical intraepithelial neoplasia: a systematic review and meta-analysis, EBioMedicine, Vol: 50, Pages: 246-259, ISSN: 2352-3964
BackgroundMethylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus(HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detectinghigh-grade cervical intra-epithelial neoplasia (CIN).MethodsWe performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women. Data were extracted induplicate and requested from authors where necessary. Random-effects models and a bivariate mixed-effectsbinary regression model were applied to determine pooled effect estimates.Findings44 studies with 8819 high-risk HPV positive women were eligible. The pooled estimates for positive methylation rate in HPV16 L1 gene were higher for high-grade CIN (≥CIN2/high-grade squamousintra-epithelial lesion (HSIL) (95% confidence interval (95%CI:72·7% (47·8–92·2))) vs. low-grade CIN(≤CIN1/low-grade squamous intra-epithelial lesion (LSIL) (44·4% (95%CI:16·0–74·1))). Pooled differencein mean methylation level was significantly higher in ≥CIN2/HSIL vs. ≤CIN1/LSIL for HPV16 L1 (11·3%(95%CI:6·5–16·1)). Pooled odds ratio of HPV16 L1 methylation was 5·5 (95%CI:3·5–8·5) for ≥CIN2/HSIL vs. ≤CIN1/LSIL (p < 0·0001). HPV16 L1/L2 genes performed best in predicting CIN2 or worse(pooled sensitivity 77% (95%CI:63–87), specificity 64% (95%CI:55–71), area under the curve (0·73(95%CI:0·69–0·77)).InterpretationHigher HPV methylation is associated with increased disease severity, whilst HPV16 L1/L2 genes demonstrated high diagnostic accuracy to detect high-grade CIN in HPV16 positive women. Direct clinical use islimited by the need for a multi-genotype and standardised ass
Xu L, Selk A, Garland SM, et al., 2019, Prophylactic vaccination against human papillomaviruses to prevent vulval and vaginal cancer and their precursors, EXPERT REVIEW OF VACCINES, Vol: 18, Pages: 1157-1166, ISSN: 1476-0584
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- Citations: 17
Mitra A, Macintyre D, Lee Y, et al., 2019, CERVICAL INTRAEPITHELIAL NEOPLASIA IS ASSOCIATED WITH AN ALTERED VAGINAL MICROBIOME AND INNATE IMMUNE DISRUPTION, Publisher: BMJ PUBLISHING GROUP, Pages: A71-A71, ISSN: 1048-891X
Semertzidou A, MacIntyre D, Marchesi J, et al., 2019, CHARACTERISATION OF THE MICROBIOME ALONG THE FEMALE GENITAL TRACT AND RECTUM IN ENDOMETRIAL CANCER, Publisher: BMJ PUBLISHING GROUP, Pages: A363-A364, ISSN: 1048-891X
Mitra A, Macintyre D, Ntritsos G, et al., 2019, THE ROLE OF THE VAGINAL MICROBIOTA IN THE REGRESSION OF UNTREATED CIN2 LESIONS, Publisher: BMJ PUBLISHING GROUP, Pages: A37-A37, ISSN: 1048-891X
Bowden S, Kalliala I, Wielscher M, et al., 2019, CERVICAL INTRAEPITHELIAL NEOPLASIA AND CERVICAL CANCER: A GENOME WIDE ASSOCIATION STUDY (GWAS) OF THE UK BIOBANK COHORT, Publisher: BMJ PUBLISHING GROUP, Pages: A59-A60, ISSN: 1048-891X
Semertzidou A, Kalliala I, Grout-Smith H, et al., 2019, DIABETES AND GYNAECOLOGICAL CANCERS: AN UMBRELLA REVIEW, Publisher: BMJ PUBLISHING GROUP, Pages: A106-A106, ISSN: 1048-891X
Tzafetas M, Mitra A, Lever S, et al., 2019, ONCOLOGICAL AND REPRODUCTIVE OUTCOMES AFTER FERTILITY-SPARING SURGERY IN WOMEN WITH CERVICAL CANCER: A SYSTEMATIC REVIEW AND META-ANALYSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A76-A77, ISSN: 1048-891X
Bowden S, Kalliala I, Veroniki A, et al., 2019, THE USE OF HUMAN PAPILLOMAVIRUS DNA METHYLATION IN CERVICAL INTRAEPITHELIAL NEOPLASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS, Publisher: BMJ PUBLISHING GROUP, Pages: A84-A86, ISSN: 1048-891X
Semertzidou A, Wheelan E, Kalliala I, et al., 2019, RISK FACTORS FOR OVARIAN CANCER: AN UMBRELLA REVIEW, Publisher: BMJ PUBLISHING GROUP, Pages: A517-A517, ISSN: 1048-891X
Tzafetas M, Mitra A, Kalliala I, et al., 2019, THE IKNIFE AND ITS APPLICATION FOR THE TREATMENT OF CERVICAL ABNORMALITIES, Publisher: BMJ PUBLISHING GROUP, Pages: A589-A589, ISSN: 1048-891X
Athanasiou A, Veroniki AA, Efthimiou O, et al., 2019, Comparative fertility and pregnancy outcomes after local treatment for cervical intra-epithelial neoplasia and stage 1a1 cervical cancer: protocol for a systematic review and network meta-analysis from the CIRCLE Group, BMJ Open, Vol: 9, ISSN: 2044-6055
Introduction: There are several local treatment methods for cervical intra-epithelial neoplasia that remove or ablate a cone-shaped part of the uterine cervix. There is evidence to suggest that these increase the risk of preterm birth and that this is higher for techniques that remove larger parts of the cervix, although the data is conflicting. We present a protocol for a systematic review and network meta-analysis that will update the evidence and compare all treatments in terms of fertility and pregnancy complications. Methods and Analysis: We will search electronic databases (CENTRAL, MEDLINE, EMBASE) from inception till October 2019, in order to identify randomised controlled trials (RCTs) and cohort studies comparing the fertility and pregnancy outcomes amongst different excisional and ablative treatment techniques and/or to untreated controls. The primary outcome will be preterm birth (PTB; <37weeks). Secondary outcomes will include severe or extreme PTB, prelabour rupture of membranes, low birth weight (<2500gr), neonatal intensive care unit admission, perinatal mortality, total pregnancy rates, 1st and 2nd trimester miscarriage. We will search for published and unpublished studies in electronic databases, trial registries and we will hand-search references of published papers. We will assess the risk of bias in RCTs and cohort studies using tools developed by the Cochrane Collaboration. Two investigators will independently assess the eligibility, abstract the data and assess the risk of bias of the identified studies. For each outcome, we will perform a meta-analysis for each treatment comparison and a network meta-analysis once the transitivity assumption holds, using the odds ratio for dichotomous data. We will use CINEMA to assess the quality of the evidence for the primary outcome.Ethics and dissemination: Ethical approval is not required. Results will be disseminated to academic beneficiaries, medical practitioners, patients and the public.PROSPE
Raglan O, Kalliala I, Markozannes G, et al., 2019, Risk factors for endometrial cancer: An umbrella review of the literature, International Journal of Cancer, Vol: 145, Pages: 1719-1730, ISSN: 0020-7136
Although many risk factors could have causal association with endometrial cancer, they are also prone to residual confounding or other biases which could lead to over‐ or underestimation. This umbrella review evaluates the strength and validity of evidence pertaining risk factors for endometrial cancer.Systematic reviews or meta‐analyses of observational studies evaluating the association between non‐genetic risk factors and risk of developing or dying from endometrial cancer were identified from inception to April 2018 using PubMed, the Cochrane database and manual reference screening. Evidence was graded strong, highly suggestive, suggestive or weak based on statistical significance of random‐effects summary estimate, largest study included, number of cases, between‐study heterogeneity, 95% prediction intervals, small study effects, excess significance bias and sensitivity analysis with credibility ceilings.We identified 171 meta‐analyses investigating associations between 53 risk factors and endometrial cancer incidence and mortality. Risk factors were categorised: anthropometric indices, dietary intake, physical activity, medical conditions, hormonal therapy use, biochemical markers, gynaecological history and smoking. Of 127 meta‐analyses including cohort studies, three associations were graded with strong evidence. Body mass index and waist‐to‐hip ratio were associated with increased cancer risk in premenopausal women (RR per 5 kg/m2 1.49; CI 1.39–1.61) and for total endometrial cancer (RR per 0.1unit 1.21; CI 1.13–1.29), respectively. Parity reduced risk of disease (RR 0.66, CI 0.60–0.74).Of many proposed risk factors, only three had strong association without hints of bias. Identification of genuine risk factors associated with endometrial cancer may assist in developing targeted prevention strategies for women at high risk.
Hall M, Savvatis K, Nixon K, et al., 2019, Maximal-effort cytoreductive surgery for ovarian cancer patients with a high tumor burden: variations in practice and impact on outcome, Annals of Surgical Oncology, Vol: 26, Pages: 2943-2951, ISSN: 1068-9265
BackgroundThis study aimed to compare the outcomes of two distinct patient populations treated within two neighboring UK cancer centers (A and B) for advanced epithelial ovarian cancer (EOC).MethodsA retrospective analysis of all new stages 3 and 4 EOC patients treated between January 2013 and December 2014 was performed. The Mayo Clinic surgical complexity score (SCS) was applied. Cox regression analysis identified the impact of treatment methods on survival.ResultsThe study identified 249 patients (127 at center A and 122 in centre B) without significant differences in International Federation of Gynecology and Obstetrics (FIGO) stage (FIGO 4, 29.7% at centers A and B), Eastern Cooperative Oncology Group (ECOG) performance status (ECOG < 2, 89.9% at centers A and B), or histology (serous type in 84.1% at centers A and B). The patients at center A were more likely to undergo surgery (87% vs 59.8%; p < 0.001). The types of chemotherapy and the patients receiving palliative treatment alone were equivalent between the two centers (3.6%). The median SCS was significantly higher at center A (9 vs 2; p < 0.001) with greater tumor burden (9 vs 6 abdominal fields involved; p < 0.001), longer median operation times (285 vs 155 min; p < 0.001), and longer hospital stays (9 vs 6 days; p < 0.001), but surgical morbidity and mortality were equivalent. The independent predictors of reduced overall survival (OS) were non-serous histology (hazard ratio [HR], 1.6; 95% confidence interval [CI] 1.04–2.61), ECOG higher than 2 (HR, 1.9; 95% CI 1.15–3.13), and palliation alone (HR, 3.43; 95% CI 1.51–7.81). Cytoreduction, of any timing, had an independent protective impact on OS compared with chemotherapy alone (HR, 0.31 for interval surgery and 0.39 for primary surgery), even after adjustment for other prognostic factors.ConclusionsIncorporating surgery into the initia
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