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ObjectivesTo assess the survival of patients who have received an operation for recurrent cervical and endometrial cancer and to determine prognostic variables for improved oncologic outcome.MethodsA retrospective multicenter analysis of the medical records of 518 patients with cervical (N = 288) or endometrial cancer (N = 230) who underwent surgery for disease recurrence and who had completed at least 1 year of follow-up.ResultsThe median survival reached 57 months for patients with cervical cancer and 113 months for patients with endometrial cancer after surgical treatment of recurrence (p = 0.036). Histological sub-type had a significant impact on overall survival, with the best outcome in endometrial endometrioid cancer (121 months), followed by cervical squamous cell carcinoma, cervical adenocarcinoma, or other types of endometrial cancer (81 vs 35 vs 35 months; pConclusionLong-term survival can be achieved via secondary cytoreductive surgery in selected patients with recurrent cervical and endometrial cancer. An excellent outcome is possible even if the recurrence site is located in the lymph nodes. The possibility of achieving complete resection should be the main criterion for patient selection.

Background: Various factors—including age, family history, inflammation, reproductive factors, and tubal ligation—modulate the risk of ovarian cancer. In this study, our aim was to establish whether women with, or at risk of developing, ovarian cancer have an imbalanced cervicovaginal microbiome. Methods: We did a case-control study in two sets of women aged 18–87 years in the Czech Republic, Germany, Italy, Norway, and the UK. The ovarian cancer set comprised women with epithelial ovarian cancer and controls (both healthy controls and those diagnosed with benign gynaecological conditions). The BRCA set comprised women with a BRCA1 mutation but without ovarian cancer and controls who were wild type for BRCA1 and BRCA2 (both healthy controls and those with benign gynaecological conditions). Cervicovaginal samples were gathered from all participants with the ThinPrep system and then underwent 16S rRNA gene sequencing. For each sample, we calculated the proportion of lactobacilli species (ie, Lactobacillus crispatus, Lactobacillus iners, Lactobacillus gasseri, and Lactobacillus jensenii), which are essential for the generation of a protective low vaginal pH, in the cervicovaginal microbiota. We grouped samples into those in which lactobacilli accounted for at least 50% of the species present (community type L) and those in which lactobacilli accounted for less than 50% of the species present (community type O). We assessed the adjusted association between BRCA1 status and ovarian cancer status and cervicovaginal microbiota community type, using a logistic regression model with a bias reduction method. Findings: Participants were recruited between Jan 2, 2016, and July 21, 2018. The ovarian cancer set (n=360) comprised 176 women with epithelial ovarian cancer, 115 healthy controls and 69 controls with benign gynaecological conditions. The BRCA set (n=220) included 109 women with BRCA1 mutations, 97 healthy controls wild type for BRCA1 and BRCA2 and 14 controls with a benign gynaecological condition wild type for BRCA1 and BRCA2. On the basis of two-dimensional density plots, receiver–operating characteristic curve analysis, and age thresholds used previously, we divided the cohort into those younger than 50 years and those aged 50 years or older. In the ovarian cancer set, women aged 50 years or older had a higher prevalence of community type O microbiota (81 [61%] of 133 ovarian cancer cases and 84 [59%] of 142 healthy controls) than those younger than 50 years (23 [53%] of 43 cases and 12 [29%] of 42 controls). In the ovarian cancer set, women younger than 50 years with ovarian cancer had a significantly higher prevalence of community type O microbiota than did age-matched controls under a logistic regression model with bias correction (odds ratio [OR] 2·80 [95% CI 1·17–6·94]; p=0·020). In the BRCA set, women with BRCA1 mutations younger than 50 years were also more likely to have community type O microbiota than age-matched controls (OR 2·79 [95% CI 1·25–6·68]; p=0·012), after adjustment for pregnancy (ever). This risk was increased further if more than one first-degree family member was affected by any cancer (OR 5·26 [95% CI 1·83–15·30]; p=0·0022). In both sets, we noted that the younger the participants, the stronger the association between community type O microbiota and ovarian cancer or BRCA1 mutation status (eg, OR for community type O for cases aged

The criteria for distinction between independent primary tumors and metastasis from one site to the other in synchronous endometrioid endometrial and ovarian carcinoma (SEO) has been a matter of dispute for a long time. In our study we performed a comprehensive clinico-pathological and molecular analysis of 22 cases of SEO. Based on conventional clinico-pathological criteria the cases were classified as independent primary tumors (10 cases) and metastasis from one location to the other (12 cases). All tumors were analyzed by NGS with a panel of 73 genes (219 kbp). Clonal origin was confirmed in all cases by at least one shared mutation in PTEN, AKT1, PIK3CA, KRAS, TP53 and ARID1A. Two patients carried germline pathogenic mutation in cancer-predisposing genes BRCA1 or BARD1. Microsatellite instable phenotype was detected in 5/22 (22.7%) SEO, but in one case only in the endometrial tumor. In conclusion, our results showed that all 22 SEOs were clonally related, irrespectively of their clinico-pathological features. Even low grade and low stage tumors classified as independent primaries, according to the conventional morphological criteria, have a clonal origin. From the practical point of view, only the conventional morphological criteria should be used for the classification (staging) of these tumors. However, molecular profiling of these tumors may have prognostic and predictive meaning.

ObjectivesInformed decisions about cancer screening require accurate knowledge regarding cancer risks and screening. This study investigates: (1) European women’s knowledge of their risk of developing breast, ovarian, cervical or endometrial cancer, (2) their knowledge about mammography screening and (3) whether an evidence-based leaflet improves their knowledge.DesignCross-sectional online intervention survey.SettingNational samples from five European countries (Czech Republic, Germany, UK, Italy and Sweden)—drawn from the Harris Interactive and the Toluna panel, respectively, in January 2017—were queried on their knowledge of age-specific risks of developing breast, cervical, ovarian or endometrial cancer within the next 10 years and of mammography screening before and after intervention.ParticipantsOf 3629 women (inclusion criteria: age 40–75 years) invited, 2092 responded and 1675 completed the survey (response rate: 61.4%).InterventionEvidence-based leaflet summarising information on age-adjusted female cancer risks, mammography and aspects of cancer prevention.Primary outcome measuresProportion of women (1) accurately estimating their risk of four female cancers, (2) holding correct assumptions of mammography screening and (3) changing their estimations and assumptions after exposure to leaflet.FindingsAcross countries, 59.2% (95% CI 56.8% to 61.6%) to 91.8% (95% CI 90.3% to 93.0%) overestimated their female cancer risks 7–33 fold (mediansacross tumours: 50.0 to 200.0). 26.5% (95% CI 24.4% to 28.7%) were aware that mammography screening has both benefits and harms. Women who accurately estimated their breast cancer risk were less likely to believe that mammography prevents cancer (pConclusionA considerable number of women in five European countries may not possess the prerequisites for an informed choice on cancer screening. Evidence-based information in patient leaflets can improve this situation.

Objective: To describe the sonographic characteristics of a lymphocele after pelvic and/or paraaortic lymphadenectomy for gynecological malignancy, analyze and identify ultrasound characteristics related to the symptomatic and asymptomatic lymphoceles. Materials and methods: This is a retrospective analysis of ultrasound examination data collected consecutively in patients after pelvic and/or paraaortic lymphadenectomy in one institution. We recorded the number of lymphoceles, localization, size; ultrasound morphology following International Ovarian Tumor Analysis group classification and symptoms. Results: We described and analyzed 227 lymphoceles (150 asymptomatic and 77 symptomatic) in 161 patients. The asymptomatic lymphocele is typically a thick-walled cystic lesion without vascularization, round and unilocular with anechoic or ground-glass content. The symptomatic lymphocele is typically an oval, or ovoid, unilocular lesion with low-level or anechoic content (ground glass content is unlikely to be present, p 1) (p = 0.005), septa (p = 0.002), and debris (p

Objective The aim of this survey was to acquire an overview of the current management of cervical cancer with an emphasis on the early disease stages. Materials and Methods A hyperlink to the survey was sent to the European Society of Gynaecological Oncology Office database. The survey contained 6 groups of questions regarding the characteristics of respondents, pretreatment workup, management of the early stages of cervical cancer, adjuvant treatment, fertility-sparing treatment, and surveillance. Results In total, 566 responses were collected. The most frequent imaging method used in the workup was magnetic resonance imaging (74%), followed by computed tomography (54%) and positron emission tomography/computed tomography (25%). Conization or simple hysterectomy was a preferred procedure in stage T1a1 lymphovascular space invasion (LVSI)–positive for 79% of respondents, in stage T1a2 LVSI-negative for 58%, and in stage T1a2 LVSI-positive for 28%. Sentinel lymph node biopsy alone was reported in stage T1a1 by 17% and in stage T1b1 less than 2 cm by 9%, whereas systematic lymphadenectomy by 29% and 90% of respondents. Macrometastases, micrometastases, and isolated tumor cells in lymph nodes were considered indications for adjuvant treatment by 96%, 93%, and 68% of respondents, respectively. Neoadjuvant chemotherapy was reported by 28% and 19% of respondents in fertility-sparing and nonsparing management in stage T1b1. Over 60% of respondents recommend primary surgery for their patients with T1b2 N0 disease and 81% of them use a combination of adverse prognostic factors as indication for adjuvant radiotherapy in pN0 disease. Conclusions The results of this survey indicate considerable differences in the workup and treatment of cervical cancer in current clinical practice.

Background Ovarian germ cell tumors (OGCT) are rare gynecological neoplasms, mostly affecting children and young women. The underlying molecular genetic background of these tumors is poorly characterized. Methods We analyzed somatic copy number aberration (CNA) profiles in 87 OGCT tumors and performed whole exome sequencing (WES) on 24 OGCT tumor and matched germline samples to further elucidate their molecular genetic landscape. Results The overall mutation rate was very low in OGCT compared to other human cancers, with an average of 0.05 mutations per Mb, consistent with their embryological origin. We identified recurrent mutations in KIT and KRAS, while CNA profiling revealed frequent focal amplifications affecting PIK3CA and AKT1 in yolk sac tumors, recurrent focal deletions affecting chromosomal regions 1p36.32, 2q11.1, 4q28.1, 5p15.33, 5q11.1 and 6q27, as well as gains in chromosome 12p that were present in all tumors, except for pure immature teratomas. Conclusion We here present the first whole exome sequencing data and to our knowledge the largest CNA study in OGCT. We confirmed that earlier reported KIT mutations were frequent in dysgerminomas and mixed forms with a dysgerminoma component, whereas chromosome 12p gains were present in all histological subtypes except pure immature teratomas. We detected recurrent KRAS mutations, recurrent focal deletions and an enrichment in the PI3K/AKT/PTEN pathway in yolk sac tumors. Several of these aberrations involve targetable pathways, offering novel treatment modalities for OGCT.

Two corrections were made to the above publication following its original online publication on 4th May 2018.

BackgroundDespite significant advances in the screening, detection, and treatment of preinvasive cervical lesions, invasive cervical cancer is the fifth most common cancer in European women. There are large disparities in Europe and worldwide in the incidence, management, and mortality of cervical cancer.ObjectiveThe European Society of Gynaecological Oncology (ESGO), the European Society for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly develop clinically relevant and evidence-based guidelines in order to improve the quality of care for women with cervical cancer across Europe and worldwide.MethodsThe ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of cervical cancer (23 experts across Europe). To ensure that the guidelines are evidence based, the current literature identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 159 international reviewers, selected through ESGO/ESTRO/ESP and including patient representatives.ResultsThe guidelines cover comprehensively staging, management, and follow-up for patients with cervical cancer. Management includes fertility sparing treatment; stage T1a, T1b1/T2a1, clinically occult cervical cancer diagnosed after simple hysterectomy; early and locally advanced cervical cancer; primary distant metastatic disease; cervical cancer in pregnancy; and recurrent disease. Principles of radiotherapy and pathological evaluation are defined.

ObjectiveThe aim of our study was to compare the sensitivity of various methods and their combinations in the follow-up of patients with cervical cancer after fertility-sparing surgery (FSS).MethodsIncluded were women with cervical cancer in stages IA2 to IB2 who underwent FSS, which includes pelvic lymphadenectomy, sentinel lymph node biopsy, abdominal radical trachelectomy, vaginal trachelectomy, or needle conization. Follow-up visits were scheduled at 3-month intervals and included symptom-oriented discussion, gynecological and physical examination, colposcopy, Papanicolaou test, human papillomavirus (HPV) DNA test, and ultrasound examination. All cases with a recurrent disease were thoroughly analyzed, and the results of individual examinations were compared.ResultsIn total, 43 women (IA2, 8; IB1, 33; IB2, 2) were enrolled. The mean patient age was 31 years; most patients were nulliparous (68.4%, 26/38) with squamous cell cancers (26/38). Abdominal radical trachelectomy was performed in 10 women, simple vaginal trachelectomy was performed in 11 women, and conization was performed in 22 women, according to the tumor characteristics and topography. The median duration of the follow-up reached 37 months. Invasive cancer and high- and low-grade squamous intraepithelial lesions were detected in 8, 1, and 1 patients, respectively. All except 1 event were central, detected within the first year after FSS. Only 2 cases were symptomatic. Colposcopy detected 7 of 10 recurrences; 5 of them were HPV positive, and, in 2 cases, a Papanicolaou test revealed abnormalities. Papanicolaou tests were false positive in 27.7%, especially after trachelectomies.ConclusionsMost patients in whom cancer recurred after FSS reveal central or pelvic lesions, which can be successfully treated with salvage surgery or radiotherapy. The early detection of recurrence is an essential condition for a favorable oncological outcome. Colposcopy alone and in combination with HPV positivity showed the highest sensitivity for the detection of recurrent diseases, whereas other methods had limited reliability.

Hepatocyte nuclear factor 1-beta (HNF-1-beta) is a transcription factor involved in cancerogenesis of various tumors, including endometrioid carcinoma. We performed comprehensive analysis of HNF-1-beta in lesions of the endometrium, including protein expression and genetic and epigenetic changes. Expression of HNF-1-beta was analyzed immunohistochemically in 320 cases including both tumor and non-tumor endometrial lesions. Promoter methylation and genetic variants were evaluated, using bisulphite and direct sequencing, in 30 (18 fresh frozen, 12 FFPE tumors) endometrioid carcinomas (ECs) and 15 ovarian clear cell carcinomas (OCCCs) as a control group. We detected expression of HNF-1-beta in 28 % of ECs (51/180 cases), 26 % of serous carcinoma (7/27 cases), 83 % of endometrial clear cell carcinoma (15/18 cases), 93 % of hyperplastic polyps with atypias (13/14 cases), 100 % of hyperplastic polyps without atypias (16/16 cases), 88 % of hyperplasias with atypias (14/16 cases), 91 % of hyperplasias without atypias (10/11 cases), and in ≥80 % of different normal endometrium samples. The control group of OCCCs showed HNF-1-beta expression in 95 % (18/19 cases). Methylation in promoter region was detected in 13.3 % (4/30) of ECs, but not in corresponding normal tissue where available, nor in OCCCs (0/15 cases). Mutation analysis revealed truncating variant c.454C > T (p.Gln152X) in one EC and missense variant c.848C > T (p.Ala283Val) was detected in one OCCC. In conclusion, expression of HNF-1-beta was detected in various extents in all types of lesions analyzed, nevertheless its strong expression was mostly limited to clear cell carcinomas. Biological significance of genetic and epigenetic changes needs further investigation.

The incidence of cancer is continuing to rise and risk-tailored early diagnostic and/or primary prevention strategies are urgently required. The ideal risk-predictive test should: integrate the effects of both genetic and nongenetic factors and aim to capture these effects using an approach that is both biologically stable and technically reproducible; derive a score from easily accessible biological samples that acts as a surrogate for the organ in question; and enable the effectiveness of risk-reducing measures to be monitored. Substantial evidence has accumulated suggesting that the epigenome and, in particular, DNA methylation-based tests meet all of these requirements. However, the development and implementation of DNA methylation-based risk-prediction tests poses considerable challenges. In particular, the cell type specificity of DNA methylation and the extensive cellular heterogeneity of the easily accessible surrogate cells that might contain information relevant to less accessible tissues necessitates the use of novel methods in order to account for these confounding issues. Furthermore, the engagement of the scientific community with health-care professionals, policymakers and the public is required in order to identify and address the organizational, ethical, legal, social and economic challenges associated with the routine use of epigenetic testing.

Ozdemir, Aykut/0000-0001-5457-3312; Basaran, Derman/0000-0002-2689-1417 WOS: 000433285800006 PubMed ID: 29770621 Objective: To evaluate the opinions of women who underwent surgery for cervical cancer (CC) and physicians who treat CC about the acceptability of increased oncological risk after less-radical surgery. Methods: One hundred eighty-two women who underwent surgery for CC and 101 physicians participated in a structured survey in 3 tertiary cancer centers in Czech Republic and Turkey. Patients and physicians were asked whether they would accept any additional oncological risks, which would be attributable to the omission of parametrectomy (radical hysterectomy/trachelectomy vs. simple hysterectomy/trachelectomy) or pelvic lymph node dissection (systematic resection vs. sentinel lymph node sampling). Results: Although 52.2% of patients reported morbidity related to their previous treatment, the majority of patients would not accept less-radical surgical treatment if it was associated with any increased risk of recurrence (50%-55%, no risk; 17%-24%, risk < 0.1%). Physicians tended to accept a significantly higher risk than patients in the Czech Republic, but not in Turkey. Patients with higher education levels, more advanced-stage of disease, or adverse events related to previous cancer treatment, and patients who received adjuvant therapy were significantly more likely to accept an increased oncological risk. Conclusion: Patients, even if they suffered from morbidity related to previous CC treatment, do not want to choose between oncological safety and a better quality of life. Physicians tend to accept the higher oncological risk associated with less-radical surgical procedures, but attitudes differ regionally. Professionals should be aware of this tendency when counselling the patients before less-radical surgery. Charles University in Prague [UNCE 204065, PROGRES-Q28/LF1]; Czech Ministry of HealthMinistry of Health, Czech Republic [MZ CR-RVO VFN64165] This work was supported by Charles University in Prague (UNCE 204065 and PROGRES-Q28/LF1) and by a project from the Czech Ministry of Health (MZ CR-RVO VFN64165).

To summarize current knowledge and recent advances in sentinel lymph node (SLN) concept in the three most frequent gynecological cancers.In cervical cancer, SLN biopsy and ultrastaging has high sensitivity in lymph node staging in patients with bilaterally detected SLN. The presence of micrometastasis is associated with shortened survival. In endometrial cancer, SLN biopsy incorporating an institutional mapping algorithm and ultrastaging has been shown to significantly reduce false-negative rates and increase sensitivity and negative predictive value.SLN biopsy and ultrastaging is useful in current management of patients with early-stage cervical cancer for multiple reasons, such as the reliable detection of key lymph nodes, identification of micrometastasis and intraoperative triage of patients. Although a complete or selective pelvic and paraaortic lymphadenectomy for adequate staging remains the standard treatment approach in patients with early-stage endometrial cancer, SLN biopsy has been shown to be safe and effective in detecting lymph node metastases. The application of the SLN procedure is safe in patients with early-stage unifocal squamous cell cancer of the vulva (4 cm) and no suspicious enlarged lymph nodes at imaging.

Summary Background The poly(ADP-ribose) polymerase inhibitor olaparib has shown antitumour activity in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer with or without BRCA1 or BRCA2 mutations. The aim of this study was to assess the efficacy and tolerability of olaparib in combination with chemotherapy, followed by olaparib maintenance monotherapy, versus chemotherapy alone in patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer. Methods In this randomised, open-label, phase 2 study, adult patients with platinum-sensitive, recurrent, high-grade serous ovarian cancer who had received up to three previous courses of platinum-based chemotherapy and who were progression free for at least 6 months before randomisation received either olaparib (200 mg capsules twice daily, administered orally on days 1–10 of each 21-day cycle) plus paclitaxel (175 mg/m 2 , administered intravenously on day 1) and carboplatin (area under the curve [AUC] 4 mg/mL per min, according to the Calvert formula, administered intravenously on day 1), then olaparib monotherapy (400 mg capsules twice daily, given continuously) until progression (the olaparib plus chemotherapy group), or paclitaxel (175 mg/m 2 on day 1) and carboplatin (AUC 6 mg/mL per min on day 1) then no further treatment (the chemotherapy alone group). Randomisation was done by an interactive voice response system, stratified by number of previous platinum-containing regimens received and time to disease progression after the previous platinum regimen. The primary endpoint was progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1, analysed by intention to treat. Prespecified exploratory analyses included efficacy by BRCA mutation status, assessed retrospectively. This study is registered with ClinicalTrials.gov, number NCT01081951, and has been completed. Findings Between Feb 12 and July 30, 2010, 173 patients at 43 investigational sites in 12 countries were enrolled into the study, of whom 162 were eligible and were randomly assigned to the two treatment groups (81 to the olaparib plus chemotherapy group and 81 to the chemotherapy alone group). Of these randomised patients, 156 were treated in the combination phase (81 in the olaparib plus chemotherapy group and 75 in the chemotherapy alone group) and 121 continued to the maintenance or no further treatment phase (66 in the olaparib plus chemotherapy group and 55 in the chemotherapy alone group). BRCA mutation status was known for 107 patients (either at baseline or determined retrospectively): 41 (38%) of 107 had a BRCA mutation (20 in the olaparib plus chemotherapy group and 21 in the chemotherapy alone group). Progression-free survival was significantly longer in the olaparib plus chemotherapy group (median 12·2 months [95% CI 9·7–15·0]) than in the chemotherapy alone group (median 9·6 months [95% CI 9·1–9·7) (HR 0·51 [95% CI 0·34–0·77]; p=0·0012), especially in patients with BRCA mutations (HR 0·21 [0·08–0·55]; p=0·0015). In the combination phase, adverse events that were reported at least 10% more frequently with olaparib plus chemotherapy than with chemotherapy alone were alopecia (60 [74%] of 81 vs 44 [59%] of 75), nausea (56 [69%] vs 43 [57%]), neutropenia (40 [49%] vs 29 [39%]), diarrhoea (34 [42%] vs 20 [27%]), headache (27 [33%] vs seven [9%]), peripheral neuropathy (25 [31%] vs 14 [19%]), and dyspepsia (21 [26%] vs 9 [12%]); most were of mild-to-moderate intensity. The most common grade 3 or higher adverse events during the combination phase were neutropenia (in 35 [43%] of 81 patients in the olaparib plus chemotherapy group vs 26 [35%] of 75 in the chemotherapy alone group) and anaemia (seven [9%] vs five [7%]). Serious adverse events were reported in 12 (15%) of 81 patients in the olaparib plus chemotherapy group and 16 of 75 (21%) patients in the chemotherapy alone group. Interpretation Olaparib plus paclitaxel and carboplatin followed by maintenance monotherapy significantly improved progression-free survival versus paclitaxel plus carboplatin alone, with the greatest clinical benefit in BRCA -mutated patients, and had an acceptable and manageable tolerability profile. Funding AstraZeneca.

To evaluate the efficacy of a collagen-fibrin patch for the prevention of symptomatic lymphoceles after pelvic lymphadenectomy in women with gynecologic malignancies.In a multicenter, randomized, clinical trial, 164 women with pelvic lymphadenectomy were allocated either to bilateral pelvic application of two collagen-fibrin patches or no intervention. Main outcome was efficacy, defined as reduction of symptomatic lymphocele rate diagnosed within four weeks after surgery. Secondary outcomes were asymptomatic lymphoceles and subsequent interventions. Sample size was based on the assumption that application of a collagen-fibrin patch reduces the prevalence of symptomatic lymphoceles by at least 66%. The study was single-blinded, i.e., patients and primary outcome assessors, but not surgeons, were blinded to the treatment allocation.A total of 75 women were randomized to the intervention and 89 to the control group. All women received the allocated intervention. In total, 42 (27.4%) lymphoceles and 8 (5.2%) symptomatic lymphoceles were observed. Symptomatic lymphoceles were observed in 5/68 (7.4%) women in the intervention group and 3/85 (3.5%) women in the control group (p = 0.47). Asymptomatic lymphoceles were observed in 16 (23.5%) women in the intervention group compared to 18 (21.2%) in the control group (p = 0.85). In a multivariate logistic regression model, no independent risk factor for the development of a symptomatic lymphocele was ascertained.Intraoperative application of collagen-fibrin patches to the pelvic side walls does not reduce the incidence of symptomatic lymphoceles in women with gynecologic malignancies undergoing pelvic lymphadenectomy.

The aim of this study was to assess the detection rate, false-negative rate and sensitivity of SLN in LN staging in tumors over 2cm on a large cohort of patients.Data from patients with stages pT1a - pT2 cervical cancer who underwent surgical treatment, including SLN biopsy followed by systematic pelvic lymphadenectomy, were retrospectively analyzed. A combined technique with blue dye and radiocolloid was modified in larger tumors to inject the tracer into the residual cervical stroma.The study included 350 patients with stages pT1a - pT2. Macrometastases, micrometastases, and isolated tumor cells were found in 10%, 8%, and 4% of cases. Bilateral detection rate was similar in subgroups with tumors2cm, 2-3.9cm, and ≥4cm (79%, 83%, 76%) (P=0.460). There were only two cases with false-negative SLN ultrastaging for pelvic LN status among those with bilateral SLN detection. The false negative rate was very low in all three subgroups of different tumor sizes (0.9%, 0.9%, and 0.0%; P=0.999). Sensitivity reached 96% in the whole group and was high in all three groups (93%, 93%, 100%; P=0.510).If the tracer application technique is adjusted in larger tumors, SLN biopsy can be equally reliable in pelvic LN staging in tumors smaller and larger than 2cm. The bilateral detection rate and false negative rate did not differ in subgroups of patients with tumors2cm, 2-3.9cm, and ≥4cm.

ObjectiveThe aim of the study was to analyze the current management of endometrial cancer across Spain and to evaluate the use and applicability of the national and international guidelines.Materials and MethodsAn electronic 30-question survey was distributed among all Spanish Society of Obstetrics and Gynecology–registered specialists dedicated to gynecologic oncology in Spain by e-mail. Data were collected anonymously and analyzed using SPSS program.ResultsOne hundred forty-five (17.8%) surveys were collected. Significant differences were observed between tertiary hospitals and secondary or private hospitals in terms of appropriate (according to European Society of Gynaecologic Oncology guidelines) nodal staging in low-risk cases (96 [95%] vs 27 [61.4%], respectively; P < 0.001), appropriate nodal staging in intermediate-risk cases (96 [95%] vs 39 [88.6%], respectively; P = 0.004), appropriate treatment in advanced-stage cases (63 [67.7%] vs 13 [40.6%], respectively; P < 0.001), and surgical treatment of relapses (87 [93.5%] vs 18 [56.3%], respectively; P = 0.004) but nonsignificant in the rate of complete paraaortic lymphadenectomy performance (82 [81.2%] vs 28 [63.6%], respectively; P = 0.056). Similar results have been observed when comparing centers with less than 20 cases per year to centers with more than 40 cases annually, with significant differences in the management of low-risk and intermediate-risk endometrial cancers.ConclusionsThis cross-sectional study demonstrates a broad heterogeneity of care giving between the clinical national and international guidelines and the actual practice in Spain. Although most of the responders refer to base their endometrial cancer management on Spanish and European Society of Gynaecologic Oncology guidelines (64.1%), many discrepancies have been observed, mainly in the management of intermediate-risk cases and follow-up. It may be caused by the lack of consensus on certain points, lack of facilities in lower case load centers, and also due to disagreement or unawareness on the current knowledge.

One of the most important principles in modern cervical cancer surgery is the concept of tailoring surgical radicality. In practice, this means abandoning the “one-fits-all” concept in favor of tailored operations. The term “radical hysterectomy” is used to describe many different procedures, each with a different degree of radicality. Anatomic structures are subjected to artificial dissection artifacts, as well as different interpretations and nomenclatures. This study aimed to refine and standardize the principles and descriptions of the different classes of radical hysterectomy as defined in the Querleu–Morrow classification and to propose its universal applicability. All three authors independently examined the current literature and undertook a critical assessment of the original classification. Images and pathologic slides demonstrating different types of radical hysterectomy were examined to document a consensual vision of the anatomy. The Cibula 3-D concept also was included in this update. The Querleu–Morrow classification is based on the lateral extent of resection. Four types of radical hysterectomy are described, including a limited number of subtypes when necessary. Two major objectives remain constant: excision of central tumor with clear margins and removal of any potential sites of nodal metastasis. Studies evaluating radicality in the surgical management of cervical cancer should be based on precise, universally accepted descriptions. The authors’ updated classification presents standardized, universally applicable descriptions of different types of hysterectomies performed worldwide, categorized according to degree of radicality, independently of theoretical considerations.

The aim of this study was to determine oncological outcomes and incidence of lymph node (LN) metastases in women who underwent systematic pelvic and paraaortic lymphadenectomy for surgical staging of apparent stage I low-grade epithelial ovarian cancer (LGEOC). A retrospective study was performed at nine institutions across Europe and the US, and patients who underwent surgical staging for presumed stage I LGEOC between 2000 and 2016 were included. To ensure surgical quality, a minimum number of ≥10 pelvic and ≥10 paraaortic LNs was required. Patients with preoperative radiologic or clinical evidence of extraovarian or LN disease, and those with nonepithelial histology, were excluded. The overall incidence of LN metastases was 4.3% in the 163 evaluated patients, and the incidence of LN involvement in serous, endometrioid, and mucinous subtypes was 10.7, 1.5, and 0%, respectively. However, Upstaging due to LN involvement alone occurred in only 2.4% of the patients. Eighty-nine (54.6%) patients received adjuvant chemotherapy due to International Federation of Gynecology and Obstetrics stage IC or higher disease. The 5-year progression-free survival (PFS) and overall survival (OS) were 93.2% (95% confidence interval [CI] 89.4–97.1%) and 94.5% (95% CI 90.9–98.0%), respectively. There was no significant difference in PFS or OS between LN-negative and LN-positive patients. However, fewer patients received adjuvant chemotherapy in the LN-negative group. Multivariate analysis did not identify any independent prognostic factor of survival. The risk of LN involvement in nonserous apparent stage I LGEOC appears low, with a rate of

ObjectiveThe aim of this study was to understand the current situation of surgical education and training in Europe among members of the European Society of Gynecological Oncology (ESGO) and its impact on the daily surgical practice of those that have completed an accredited fellowship in gynecologic oncology.MethodsA questionnaire addressing topics of interest in surgical training was designed and sent to ESGO members with surgical experience in gynecologic oncology. The survey was completely confidentially and could be completed in less than 5 minutes. Responses from 349 members from 42 European countries were obtained, which was 38% of the potential target population. The respondents were divided into 2 groups depending on whether they had undergone an official accreditation process.ResultsTwo thirds of respondents said they had received a good surgical education. However, accredited gynecologists felt that global surgical training was significantly better. Surgical self-confidence among accredited specialists was significantly higher regarding most surgical oncological procedures than it was among their peers without such accreditation. However, the rate of self-assurance in ultraradical operations, and bowel and urinary reconstruction was quite low in both groups. There was a general request for standardizing surgical education across the ESGO area. Respondents demanded further training in laparoscopy, ultraradical procedures, bowel and urinary reconstruction, and postoperative management of complications. Furthermore, they requested the creation of fellowship programs in places where they are not now accredited and the promotion of rotations and exchange in centers of excellence. Finally, respondents want supporting training in disadvantaged countries of the ESGO area.ConclusionsSpecialists in gynecologic oncology that have obtained a formal accreditation received a significantly better surgical education than those that have not. The ESGO responders recognize that their society should lead the standardization of surgical training and promote ways of improving members’ surgical skills.

The Czech Republic ranks among the countries with the highest cancer burden in Europe as well as worldwide. The purpose of this study is to summarize longterm trends in the cancer burden and to provide up-to-date estimates of incidence and mortality rates after 2011.The Czech National Cancer Registry (CNCR) was instituted in 1977 and contains information collected over a 34-year period of standardized registration covering 100% of cancer diagnoses within the entire Czech population. The CNCR analysis is supported by demographic data and by the Death Records Database. An overview of the epidemiology of malignant tumors in the Czech population is available online at www.svod.cz.All neoplasms, including nonmelanoma skin cancer, reached a crude incidence rate of almost 802 cases per 100,000 men and 681 cases per 100,000 women in 2011. The annual mortality rate exceeded 258 deaths per 100,000 individuals; in other words, more than 27,000 individuals die of cancer each year. The overall incidence of malignancies has increased with a growth index of +27.6% during the last decade (2001- 2011), while the mortality rate has been stabilized over the time span (growth index in 2001- 2011: - 5.0%). Consequently, the prevalence has significantly increased in the observed period and exceeded 475,000 cases in 2011. In addition to demographic aging of the Czech population, the cancer burden has also increased due to the growing incidence of multiple primary tumors (recently more than 15% of the total incidence). The most frequent diagnoses include colorectal cancer, lung cancer, breast cancer, and prostate cancer. Although some neoplasms are increasingly diagnosed at an early stage (e. g. the proportion of stage I or II was 75.3% for female breast cancer and 84.2% for skin melanoma), the numbers of early diagnosed cases are generally insufficient, even in the case of highly prevalent cancers such as colorectal carcinoma (only 46.1% of incident cases are diagnosed at stage I or II, according to recent data).Population-based data on malignant tumors are available in the Czech Republic. The data survey can help us define national cancer management priorities. The current priority is to achieve a sustained reduction of cases diagnosed at an advanced stage and reduction of the significant regional differences in diagnostic efficiency.

Objectives To identify major factors in the under- and overestimation of cervical and myometrial invasion by endometrial cancer at preoperative staging by ultrasound. Methods This prospective study involved all patients with histologically confirmed endometrial cancer referred consecutively for surgical staging between January 2009 and December 2011. All patients underwent transvaginal ultrasound examination, obtaining metric and perfusion data, and the results were compared with final histology: myometrial invasion was defined at histology in the final pathology report as being either = 50%, while cervical stromal invasion was reported as being either present or absent, and sonographic over-/underestimation was determined relative to these. Results Enrolled prospectively into the study were 210 patients. The proportion of cases with sonographic underestimation, relative to final histology, of myometrial invasion (i.e. false-negative estimation of no or superficial invasion < 50%) and of cervical invasion (i.e. false-negative finding of absence of stromal invasion) was comparable: 8.6% (n=18) and 10.5% (n=22), respectively. Myometrial invasion was overestimated by ultrasound (i.e. false-positive estimation of deep invasion >= 50%) in 15.7% (n=33) of cases, and cervical invasion was overestimated (i.e. false-positive finding of presence of stromal invasion) in 4.8% (n=10) of cases. These outcomes correspond to positive and negative predictive values of 67.6% (95% CI, 57.7-76.6) and 83.3% (95% CI, 74.9-89.8), respectively, for the subjective assessment of myometrial invasion, and 60.0% (95% CI, 38.2-79.2) and 88.1% (95% CI, 82.5-92.4), respectively, for that of cervical stromal invasion. The staging error in subjective assessment was not related to body mass index (BMI), to the position of the uterus in the pelvis or to image quality. Cervical and myometrial invasion were more often underestimated in well-differentiated endometrial cancers that were smaller in size, with thick minimum tumor-free myometrium and lower perfusion, and more often overestimated in moderately and poorly differentiated cancers that were larger in size, with thin minimum tumor-free myometrium and richer perfusion. Conclusion The accuracy of subjective assessment of myometrial and cervical invasion by ultrasound was significantly influenced by tumor size, density of tumor vascularization, tumor vessel architecture and histological grading, while it was not significantly affected by BMI, uterine position and image quality.

Item does not contain fulltext The accurate harvesting of a sentinel node in gynaecological cancer (i.e. vaginal, vulvar, cervical, endometrial or ovarian cancer) includes a sequence of procedures with components from different medical specialities (nuclear medicine, radiology, surgical oncology and pathology). These guidelines are divided into sectione entitled: Purpose, Background information and definitions, Clinical indications and contraindications for SLN detection, Procedures (in the nuclear medicine department, in the surgical suite, and for radiation dosimetry), and Issues requiring further clarification. The guidelines were prepared for nuclear medicine physicians. The intention is to offer assistance in optimizing the diagnostic information that can currently be obtained from sentinel lymph node procedures. If specific recommendations given cannot be based on evidence from original scientific studies, referral is made to "general consensus" and similar expressions. The recommendations are designed to assist in the practice of referral to, and the performance, interpretation and reporting of all steps of the sentinel node procedure in the hope of setting state-of-the-art standards for high-quality evaluation of possible metastatic spread to the lymphatic system in gynaecological cancer. The final result has been discussed by a group of distinguished experts from the EANM Oncology Committee and the European Society of Gynaecological Oncology (ESGO). The document has been endorsed by the SNMMI Board.

One randomized study by Ramirez et al and one epidemiological study by Melamed et al[1 2][1] found that the minimal invasive surgery approach for radical hysterectomy for cervical cancer is associated with shorter disease-free and overall survival than open surgery. These findings were confirmed in

Background Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer and is often diagnosed at advanced stages. The current standard of care (SOC) for advanced EOC is primary debulking surgery (PDS) followed by adjuvant carboplatin/paclitaxel chemotherapy (CT). Although SOC may be effective initially, most patients experience relapse within 3 years after treatment. Combination therapy with PD-1 inhibitor pembrolizumab (pembro) plus PARP inhibitor niraparib resulted in efficacy in patients with platinum-resistant, relapsed OC in the phase 1/2 study TOPACIO/KEYNOTE-162. The PARP inhibitor olaparib is approved for women with newly diagnosed BRCA-mutated OC, as well as for platinum-sensitive, recurrent OC regardless of BRCA1/2 status. Pembro plus CT followed by olaparib maintenance therapy is being investigated in ENGOT-ov43/KEYLYNK-001 (NCT03740165), a phase 3, randomized, double-blind, active- and placebo-controlled study for first-line treatment of women with BRCA1/2-nonmutated advanced EOC. Trial design Women with stage III or IV BRCA-nonmutated EOC, primary peritoneal cancer, or fallopian tube cancer will be randomized 1:1:1 after one lead-in cycle of CT to receive pembro + CT followed by olaparib maintenance; pembro + CT followed by placebo; or placebo + CT followed by placebo. Stratification factors include surgery status (residual tumor after PDS [yes/no] or planned interval debulking), planned bevacizumab use (yes/no), and PD-L1 combined positive score (CPS; Clinical trial identification NCT03740165. Legal entity responsible for the study Merck & Co., Inc. Funding Funding for this study was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Disclosure K. Fujiwara: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharpe & Dohme Corp.; Advisory / Consultancy, Research grant / Funding (institution): Pfizer; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy: Takeda; Honoraria (self): Bayer; Honoraria (self): Daiichi Sankyo; Honoraria (self): Janssen Oncology; Honoraria (self): Kyowa Hakko Kirin; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self): Nippon Kayaku; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self): Zeria Pharmaceutical; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Immunogen; Research grant / Funding (institution): Kaken Pharmaceutical; Research grant / Funding (institution): Oncotherapeutics; Research grant / Funding (institution): Shionogi. I.B. Vergote: Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Advaxis; Advisory / Consultancy: Merck Sharp & Dohme Corp.; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Genmab; Advisory / Consultancy: Millennium Pharmaceuticals; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy: Immunogen; Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Advisory / Consultancy, Research grant / Funding (institution): Oncoinvent; Advisory / Consultancy: Roche; Advisory / Consultancy: Sotio; Travel / Accommodation / Expenses: Takeda; Research grant / Funding (institution): Amgen. J. Sehouli: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Eisai; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Clovis; Honoraria (self): Olympus; Honoraria (self): JohnsonJ Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Honoraria (self): Teva Pharmaceutical Industries Ltd.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Merck Sharpe & Dohme Corp.; Advisory / Consultancy: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche. P. Zola: Advisory / Consultancy, Travel / Accommodation / Expenses: TESARO, Inc.; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Roche. R.M. Wenham: Research grant / Funding (self), Shareholder / Stockholder / Stock options: Ovation Diagnostics; Advisory / Consultancy, Speaker Bureau / Expert testimony: TESARO, Inc.; Advisory / Consultancy: Merck; Advisory / Consultancy, Speaker Bureau / Expert testimony: Clovis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech; Advisory / Consultancy: Mersana Therapeutics; Research grant / Funding (self): TapImmune; Research grant / Funding (self): Merck; Research grant / Funding (self): Prescient Therapeutics. P. Pautier: Advisory / Consultancy: Roche; Advisory / Consultancy, Travel / Accommodation / Expenses: PharmaMar; Advisory / Consultancy: GlaxoSmithKline. S. Lheureux: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): TESARO, Inc.; Research grant / Funding (institution): Roche/Genentech; Research grant / Funding (institution): Regeneron. K. Hasegawa: Honoraria (self), Research grant / Funding (self): Daiichi-Sankyo; Honoraria (self): Chugai; Honoraria (self), Advisory / Consultancy: Merck Sharpe & Dohme Corp.; Honoraria (self): AstraZeneca; Research grant / Funding (self): Yakult Honsha; Research grant / Funding (self): Pfizer. C-H. Lai: Research grant / Funding (self): Roche; Research grant / Funding (self): TTY Biopharm. A. Gonzalez-Martinez: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Merck Sharpe & Dohme Corp.; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): TESARO, Inc.; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pharmama. Q. Liu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. S.M. Keefe: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. M. Puglisi: Shareholder / Stockholder / Stock options, Full / Part-time employment: Merck & Co., Inc. All other authors have declared no conflicts of interest.

Background Tumour Treating Fields (TTFields) are a non-invasive, regional antimitotic therapy. In preclinical models of ovarian cancer, TTFields (200 kHz) reduced cell viability and showed synergistic effects with taxanes in vitro and in vivo. The Phase 2 INNOVATE study [NCT02244502] demonstrated safety of TTFields plus weekly paclitaxel in 31 PROC (platinum-resistant ovarian cancer) patients (Vergote et al Gyn Onc 2018;150:471). No increase in grade 3–4 TTFields were reported; 26 patients (84%) had TTFields-related dermatitis; one patient permanently discontinued TTFields due to dermatitis. Patients received median of 4 prior therapies; 100% prior platinum and 97% prior taxanes. Median PFS was 8.9 months, 25% had partial response and clinical benefit rate was 71%. The median overall survival was not reached: the one-year survival rate was 61%. This phase 3 INNOVATE-3/ENGOT-ov50 study [NCT03940196] investigates TTFields combined with weekly paclitaxel in PROC patients. Trial design Patients (N = 540) will have disease progression (PROC per RECIST V1.1) within 6 months of last platinum therapy with a maximum of 2-5 prior lines of systemic therapy, ECOG score of 0-1 and no peripheral neuropathy above grade1. Patients with primary refractory disease (progression during first line therapy) will be excluded. Patients will be randomized 1:1 to either weekly paclitaxel alone or weekly paclitaxel plus TTFields (200 kHz). Weekly paclitaxel will be administered at standard starting of dose 80 mg/m2 weekly for 8 weeks, and then on Days 1, 8, and 15 for subsequent 28-day cycle. TTFields will be delivered for 18 hours/day and continued if no progression in the abdominal or pelvic regions (“in-field region”) per RECIST V1.1. Clinical follow up will be performed q4w, with radiological follow up (CT or MRI scans of the abdomen and chest) q8w. The primary endpoint is overall survival. Main secondary endpoints: progression-free survival, objective response rate, severity and frequency of AEs, and quality of life (EORTC QLQ-C30 with QLQ-OV28). Sample size (n = 540) will detect an increase in median overall survival from 12 to 16 months (Hazard ratio 0.75). Clinical trial identification ENGOT/ov50; NCT03940196. Legal entity responsible for the study Novocure. Funding Novocure. Disclosure I.B. Vergote: Advisory / Consultancy: Roche NV, Genmab A/S, Advaxis Inc., Morphotek Inc., F. Hoffmann-La Roche Ltd.; Research grant / Funding (institution): Amgen and Roche; Advisory / Consultancy: Cerculean Pharma Inc., Novocure GmBh, AstraZeneca,; Advisory / Consultancy: Mateon Therapeutics Inc., Immunogen; Advisory / Consultancy: Eli Lilly Benelux NV, Amgen Inc., Theradex Europe; Advisory / Consultancy: Pfizer Inc., Debiopharma International SA, Vifor Pharma Belgie; Advisory / Consultancy: Novartis Pharma AG, MSD Belgium BVBA, Janssen-Cilag; Advisory / Consultancy: Bayer Pharma AG, Clovis Oncology, Takeda, Pharma Mar, Oncoinvent; Travel / Accommodation / Expenses: Tesaro, Clovis Oncology, Takeda,; Travel / Accommodation / Expenses: Pharma Mar, Roche, Genmab and Oncoinvent. D. Cibula: Advisory / Consultancy: Roche, AstraZeneca, Sotio. V. Salutari: Honoraria (self) / Advisory role / Speaker Bureau: Roche, AstraZeneca, Tesaro, PharmaMar, MSD, Clovis. All other authors have declared no conflicts of interest.

TPS5603 Background: There is a significant unmet need to develop new regimens for BRCA1/2-nonmutated advanced ovarian cancer (OC). The PARP inhibitor olaparib is approved for women with platinum-sensitive, recurrent OC regardless of BRCA1/2 status and, more recently, for newly diagnosed women with BRCA-mutated OC. In the TOPACIO/KEYNOTE-162 study, the combination of the PD-1–blocking antibody pembrolizumab (pembro) and niraparib demonstrated efficacy in platinum-resistant relapsed OCirrespective of BRCA1/2 status. ENGOT-OV43/KEYLYNK-001 (ClinicalTrials.gov, NCT03740165) is a phase 3, randomized, double-blind, active- and placebo-controlled study of pembro plus paclitaxel-carboplatin chemotherapy (CT) followed by olaparib maintenance for first-line treatment of patients with BRCA1/2-nonmutated advanced epithelial OC (EOC). Methods: Patients with stage III or IV BRCA-nonmutated EOC, primary peritoneal cancer, or fallopian tube cancer will be stratified by surgery status (no residual tumor after primary debulking surgery [PDS], residual tumor after PDS, or planned interval debulking), bevacizumab use, and PD-L1 status (combined positive score < 10 or ≥10). After one lead-in cycle of CT, patients will be randomized 1:1:1 to receive: CT + pembro followed by olaparib maintenance; CT + pembro followed by placebo; or CT + placebo followed by placebo. The CT regimen will be administered for 5 cycles, and pembro 200 mg Q3W will be administered for 35 infusions. Olaparib 300 mg BID maintenance therapy will start after the end of CT as concomitant treatment with pembro until discontinuation or for 2 years if the patient has a complete response. Bevacizumab use is permitted at investigator’s discretion and determined prerandomization. Primary endpoints are investigator-assessed progression-free survival (PFS) per RECIST 1.1 criteria and overall survival. Key secondary endpoints are PFS per RECIST 1.1 assessed by blinded independent central review, PFS after next-line treatment, and safety. Enrollment is currently ongoing. Clinical trial information: NCT03740165.

TPS5600 Background: Despite surgery and SOC therapy (paclitaxel and carboplatin ± bevacizumab[bev]), 5-year survival rates remain low for patients (pts) with FIGO stage 3/4 OC. Niraparib (ZEJULA) is the first selective poly(ADP-ribose) polymerase inhibitor (PARPi) approved in the US and Europe for maintenance treatment in pts with recurrent OC regardless of BRCAmut status. Preclinical data suggest synergy with PARPi + anti-PD-1 blockade. Niraparib + pembrolizumab has shown clinical efficacy in pts with platinum-resistant or secondary refractory OC regardless of biomarker status. Dostarlimab is an anti–PD-1 humanized monoclonal with clinical activity as monotherapy in early phase trials. The primary objective of the currently enrolling FIRST trial is to compare PFS (per RECIST v1.1) in pts treated with SOC + dostarlimab + niraparib to SOC. Methods: Eligible pts (up to 912) are FIGO stage 3 (with residual disease, CC0 high risk, or planned neoadjuvant therapy) or stage 4, non-mucinous epithelial OC and ECOG score < 2. After 1 cycle of SOC, pts are stratified by concurrent bev use, BRCAmut/HRR status, and disease burden then randomized as 1:1:2 to 1 of 3 arms (Table). An innovative feature of ENGOT-OV44/FIRST (NCT03602859; EUDRACT 2018-000413-20) is the pre-planned adaptive study design to adapt the control arm to the evolving SOCs in OC, allowing pts in the control arm to receive up to date SOC. These adaptations will occur when practice-changing data are released. Following publication of SOLO1 results, BRCAmut pts will only be randomized to arm 2 or 3 to ensure they receive niraparib. Further adaptations may be incorporated as new data become available, leading to stop randomization in arm 1 or 2 of pts based on their biomarker status. Clinical trial information: NCT03602859. [Table: see text]

5506 Background: Data from a randomized Phase II trial (NCT00628251) of olaparib (capsules, 200 or 400 mg bid, n=32 per arm) vs pegylated liposomal doxorubicin (PLD, n=33) in gBRCAm OC pts with recurrence ≤12 months after prior platinum therapy indicated efficacy for olaparib (Kaye et al. JCO 2012). However, the efficacy of PLD was higher than previously reported in this setting. We led a confirmatory Phase III, open-label study of olaparib vs non-platinum chemotherapy in gBRCAm PSR OC pts (NCT02282020). Methods: Pts were randomized (2:1) to olaparib tablets (300 mg bid) or chemotherapy treatment of physician’s choice (TPC) (paclitaxel [P; 80 mg/m2 on day 1 (D1), D8, D15, D22 every 4 weeks (q4w)], topotecan [T; 4 mg/m2 D1, D8, D15 q4w], gemcitabine [G; 1000 mg/m2 D1, D8, D15 q4w] or PLD [50 mg/m2 D1 q4w]) until progression, stratified by: TPC, prior lines of chemotherapy (2–3 vs ≥4) and platinum-free interval (6–12 vs >12 months). Primary endpoint: ORR (blinded independent central review [BICR]). Secondary endpoints included PFS and safety. Results: 266 gBRCAm PSR OC pts were randomized (olaparib, n=178; TPC, n=88 [ PLD, n=47; P, n=20; G, n=13; T, n=8]); 12 in the TPC arm withdrew before receiving study treatment. 223 pts (84%) had baseline BICR measurable disease (olaparib, n=151; TPC, n=72). ORR was 72% with olaparib vs 51% with TPC (OR 2.53, 95% CI 1.40–4.58; P=0.002). HR for PFS by BICR was 0.62 (95% CI 0.43–0.91; P=0.013; median 13.4 vs 9.2 months [olaparib vs TPC]) and by investigator assessment was 0.49 (95% CI 0.35–0.70; P

A lymphocele is a cystic mass that may occur in the retroperitoneum following a systematic pelvic and/or para-aortic lymphadenectomy. Lymphoceles may be the cause of severe morbidity, or rarely mortality. Symptomatic lymphoceles manifest with pain, compression of adjacent structures, lymphoedema, deep vein thrombosis or inflammation. The morbidity associated with a symptomatic lymphocele may reduce the quality of life of a patient, as well as delay subsequent cancer treatment. The number and positivity of removed lymph nodes, surgical approach, type of tumor, radiotherapy and BMI rate are among the most discussed risk factors of lymphocele formation. The incidence of postoperative lymphocele is reported in the broad range of 1-58%; 5-18% of those who are symptomatic. Only symptomatic lymphoceles should be treated. Mini-invasive methods involving catheter drainage and sclerotization tend to prevail. Surgery either via laparoscopy or laparotomy remains an option in recurring, poorly accessible or inflammatory lymphoceles.

Background: The objective of this study was to assess trends in overall and in stage-specific 5-year relative survival rates of the Czech cancer patients between periods 2000-2004 and 2005-2008. Methods: All Czech cancer patients diagnosed between 1995 and 2008 were included in the analysis. Period analysis was employed to calculate 5-year relative survival for 21 cancers. Results: Significant improvements in crude 5-year relative survival for 14 of 21 assessed types of cancer, including the most frequent diagnoses, such as, colorectal, prostate, breast, lung, kidney, pancreatic, and bladder cancer and melanoma, were identified. Moreover, in case of colorectal, lung, and prostate cancer, improvement in stage-specific 5-year relative survival was confirmed as statistically significant for all clinical stages. No diagnosis showed significant decrease in the 5-year relative survival. However, the 5year relative survival remained poor in patients with metastatic cancers at diagnosis, particularly in case of liver, pancreatic, lung, and oesophageal cancer. Conclusions: The cancer-specific outcomes in the Czech Republic are improving. Nevertheless, despite the overall significant improvement in 5-year relative survival of most of the cancer diagnoses, the high proportion of patients primarily diagnosed with metastatic cancer still represents a substantial challenge for prevention and early detection.

Background More than 90% of cases of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) is established as possible risk factor. Objectives To demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer. Study design A total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy-confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Cobas and Lynear array HPV test. Results Cervical, anal, and concurrent cervical and anal HPV infections were detected in 82.6%, 48.3% and 42.4% of women in the study group, and in 28.0%, 26.0% and 8.0% of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections of the cervix and anus occurred 5.3-fold more often in the study group than in the control group. Any contact with the anus was the only significant risk factor for development of concurrent HPV infection. Conclusions Concurrent anal and cervical HR HPV infection was found in nearly half of women with CIN 2+. The dominant genotype found in both anatomical locations was HPV 16. Any frequency and any type of contact with the anus were shown as the most important risk factor for concurrent HPV infection.

Objectives To assess the accuracy of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) in the evaluation of tumor size and in the detection of residual tumor following neoadjuvant chemotherapy (NACT) in patients with cervical cancer. Methods This was a prospective study involving 42 women with locally advanced histologically confirmed cervical cancer referred for NACT. Clinical examination, TRUS and MRI were performed before and after NACT. The tumor volume was calculated using three standardized diameters (anteroposterior, laterolateral and craniocaudal) that were measured using both TRUS and MRI. Thereafter patients underwent surgical treatment and the same tumor measurements were taken by a pathologist using a fixed surgical specimen. Tumor volumes were calculated from tumor dimensions using the ellipsoid formula, and data obtained from both imaging methods were compared with pathological results as the gold standard. Results Twelve cases were excluded from the study owing to disease progression (these patients were referred for primary radiotherapy) or inability to perform MRI, leaving data from 30 patients for the final analysis. On average, tumor volume decreased after NACT by 84.6 and 87.1% as measured by MRI and TRUS, respectively. The agreement between measurements obtained by MRI and histology did not reach significance (intraclass correlation coefficient, 0.344 (95% CI, –0.013 to 0.610), P = 0.059), while agreement between TRUS and histology was statistically significant (intraclass correlation coefficient, 0.795 (95% CI, 0.569–0.902), P 5 mm3 in volume) reached 77% for both MRI and TRUS. The sensitivity of TRUS was, however, lower than that of MRI (83 vs 96%). The positive predictive values were similar for the two methods. Conclusions TRUS should be considered as an accurate diagnostic method in the evaluation of tumor volume after NACT in patients with cervical cancer and may constitute a reliable alternative imaging method to MRI. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Objectives Metastatic involvement of the sentinel nodes (SN) is one of the main prognostic factors in cervical cancer which determines the disease management. The results of intra-operative SN examination would make it possible to triage patients in a one-step protocol. The studies carried out on the subject so far have, however, failed to demonstrate adequate accuracy of frozen section examination (FS) and, moreover, they only involved small cohorts. Methods The study included 225 patients with cervical cancer FIGO IA2–IIB in whom at least one SN has been detected and intra-operatively processed. The prevalence of macrometastases, micrometastases and isolated tumour cells (ITC) in the SN was evaluated and the results of FS and final SN ultrastaging were compared. Results Metastatic involvement of the SN was detected by pathologic ultrastaging in 73 cases (32.4%); macrometastases, micrometastases and ITC were found in 48, 17 and 8 patients, respectively. Intra-operative SN assessment established the SN status correctly in as few as 41 cases (56.2%), or in 49 cases (63%) if ITC had been excluded. Final ultrastaging of intra-operatively negative SN confirmed macrometastases, micrometastases, and ITC in additional 8, 18 and 8 patients, respectively. The false negative rate of FS was higher in bigger tumours (>20cm 3 ) and in the presence of LVSI. Conclusions Frozen section examination of SN is not sufficiently reliable; it has a high false negative rate mainly due to its limited ability to detect micrometastases. A possible solution would be a more detailed intra-operative pathologic processing or two-step surgical management.

AIM: This study was designed to evaluate feasibility and effectiveness of hysteroscopic intervention in the management of symptoms related to the displaced levonorgestrel-releasing intrauterine system (LNG-IUS). MATERIAL AND METHODS: One hundred and thirteen patients with displaced LNG-IUS presenting with irregular uterine bleeding pelvic pain or asymptomatic displacement were recruited for hysteroscopic examination. Displaced LNG-IUS was relocated by hysteroscopic intervention and the effect on symptoms and LNG-IUS position was followed. RESULTS: The displaced LNG-IUS was successfully relocated by hysteroscope in 112 (99.1%) of 113 cases. Following LNG-IUS relocation 71 (79.8%) patients of 89 with preoperative irregular uterine bleeding had amenorrhea or vaginal spotting and 14 of 15 (93.3%) patients with preoperative pelvic pain became asymptomatic. LNG-IUS expulsion was recorded in two patients 7 and 21 days after hysteroscopy. CONCLUSION: Displaced LNG-IUS can cause clinical symptoms (e.g. irregular bleeding pain). Hysteroscopic relocation of displaced LNG-IUS is a feasible method in the management of these symptoms. Risk of spontaneous expulsion associated with hysteroscopy is low. (c) 2013 The Authors. Journal of Obstetrics and Gynaecology Research (c) 2013 Japan Society of Obstetrics and Gynecology.

To compare the diagnostic accuracy of ultrasound (US) and magnetic resonance imaging (MRI) in the preoperative assessment of early-stage cervical cancer using pathologic findings as the reference standard.Prospective multi-center trial enrolling 209 consecutive women with early-stage cervical cancer (FIGO IA2-IIA) scheduled for surgery. The following parameters were assessed on US and MRI and compared to pathology: remaining tumor, size, tumor stromal invasion2/3 (superficial) or ≥2/3 (deep), and parametrial invasion.Complete data were available for 182 patients. The agreement between US and pathology was excellent for detecting tumors, correctly classifying bulky tumors (4cm), and detecting deep stromal invasion (kappa values 0.84, 0.82, and 0.81 respectively); and good for classifying small tumors (2cm) and detecting parametrial invasion (kappa values 0.78 and 0.75, respectively). The agreement between MRI and histology was good for classifying tumors as2cm, or4cm, and detecting deep stromal invasion (kappa values 0.71, 0.76, and 0.77, respectively). It was moderately accurate in tumor detection, and in assessing parametrial invasion (kappa values 0.52 and 0.45, respectively). The agreement between histology and US was significantly better in assessing residual tumor (p0.001) and parametrial invasion (p0.001) than the results obtained by MRI. Imaging methods were not significantly influenced by previous cone biopsy.US and MRI are highly accurate for the preoperative assessment of women with early-stage cervical cancer, although US may be more accurate in detecting residual tumors and assessing parametrial invasion.

5500 Background: So far, there is no level-1 evidence regarding the role of systematic pelvic and para-aortic lymphadenectomy (LNE) in patients with advanced ovarian cancer (AOC) with macroscopic complete resection und clinically negative lymph nodes (LN). Therefore, surgical management regarding LNE worldwide is very heterogeneous. Methods: Prospective randomized trial including patients with newly diagnosed AOC FIGO IIB-IV with macroscopic complete resection and pre- and intra-operatively clinical negative LN were randomized intra-operatively to LNE versus no-LNE. All centers had to qualify regarding surgical skills before participation in this trial. The primary endpoint was overall survival. Results: 647 patients were randomized between 12/08 and 1/12 to LNE (n=323) or no-LNE (n=324). The median number of removed LN in patients randomized to LNE was 57 (pelvic 35 and para-aortic22). Post-op platinum-taxane based chemotherapy was applied in 85% of the patients in the no-LNE arm and 80% in the LNE arm. Microscopic metastases were diagnosed in 56% of the pts in the LNE arm. Median OS in the no-LNE arm was 69 months and 66 months in the LNE arm (HR 1.06, 95%CI 0.83-1.34, p=0.65) and the median PFS was 26 months in both arms (HR 1.11, 95%CI 0.92-1.34 p=0.30). Surgery in the LNE arm was 64 minutes longer (means: 352 vs 288 min), resulted in a higher median blood loss (650 vs 500 ml), and a higher transfusion rate (67% vs 59%). Furthermore, serious post-operative complications occurred more frequently in the LNE arm (e.g. rate of re-laparotomies 12.1% vs 5.9% [p=0.006], hospital re-admittance rate 8.0% vs 3.1% [p=0.006] and deaths within 60 days after surgery 3.1 vs 0.9% [p=0.049]). Conclusions: Systematic pelvic and para-aortic LNE in patients with AOC with both intra-abdominal complete resection and clinically negative LN neither improve overall nor progression-free survival despite detecting (and removing) sub-clinical retroperitoneal lymph node metastases in 56% of the patients. Our data indicate that systematic LNE of clinical negative LN in patients with AOC and complete resection should be omitted to reduce post-operative morbidity and mortality. Clinical trial information: NCT00712218.

Objective To describe the technique and report experiences with pelvic floor reconstruction by modified rectus abdominis myoperitoneal (MRAM) flap after extensive pelvic procedures. Methods Surgical technique of MRAM harvest and transposition is carefully described. The patients in whom pelvic floor reconstruction with MRAM after either infralevator pelvic exenteration and/or extended lateral pelvic sidewall excision was carried out were enrolled into the study (MRAM group, n =16). Surgical data, post-operative morbidity, and disease status were retrospectively assessed. The results were compared with a historical cohort of patients, in whom an exenterative procedure without pelvic floor reconstruction was performed at the same institution (control group, n =24). Results Both groups were balanced in age, BMI, tumor types, and previous treatment. Substantially less patients from the MRAM group required reoperation within 60days of the surgery (25% vs. 50%) which was due to much lower rate of complications potentially related to empty pelvis syndrome (1 vs. 7 reoperations) ( p =0.114). Late post-operative complication rate was substantially lower in the MRAM group (any grade: 79% vs. 44%; grade≥3: 37% vs. 6%) ( p =0.041). The performance status 6months after the surgery was ≤1 in the majority of patients in MRAM (81%) while in only 38% of patients from the control group ( p =0.027). There was one incisional hernia in MRAM group while three cases were reported in the controls. Conclusions Pelvic floor reconstruction by MRAM in patients after pelvic exenterative procedures is associated with a substantial decrease in postoperative complications that are potentially related to empty pelvis syndrome.

ObjectivesThe surgical management of advanced ovarian cancer involves complex surgery. Implementation of a quality management program has a major impact on survival. The goal of this work was to develop a list of quality indicators (QIs) for advanced ovarian cancer surgery that can be used to audit and improve the clinical practice. This task has been carried out under the auspices of the European Society of Gynaecologic Oncology (ESGO).MethodsQuality indicators were based on scientific evidence and/or expert consensus. A 4-step evaluation process included a systematic literature search for the identification of potential QIs and the documentation of scientific evidence, physical meetings of an ad hoc multidisciplinarity International Development Group, an internal validation of the targets and scoring system, and an external review process involving physicians and patients.ResultsTen structural, process, or outcome indicators were selected. Quality indicators 1 to 3 are related to achievement of complete cytoreduction, caseload in the center, training, and experience of the surgeon. Quality indicators 4 to 6 are related to the overall management, including active participation to clinical research, decision-making process within a structured multidisciplinary team, and preoperative workup. Quality indicator 7 addresses the high value of adequate perioperative management. Quality indicators 8 to 10 highlight the need of recording pertinent information relevant to improvement of quality. An ESGO-approved template for the operative report has been designed. Quality indicators were described using a structured format specifying what the indicator is measuring, measurability specifications, and targets. Each QI was associated with a score, and an assessment form was built.ConclusionsThe ESGO quality criteria can be used for self-assessment, for institutional or governmental quality assurance programs, and for the certification of centers. Quality indicators and corresponding targets give practitioners and health administrators a quantitative basis for improving care and organizational processes in the surgical management of advanced ovarian cancer.

Objective The aim of our study was to describe oncological and obstetrical outcomes in patients who underwent less radical fertility-sparing surgical (FSS) procedures with omitted parametrectomy for cervical cancer. Methods Included were women with cervical cancer stages IA2–IB2 who were under the age of 40 and desired future pregnancy. Patients underwent pelvic lymphadenectomy and sentinel lymph node biopsy. Node-negative cases underwent subsequent cervical surgery and were further analyzed. Neoadjuvant chemotherapy (NAC) was administered in patients with tumors >2cm and/or involving >2/3 of cervical stroma. Simple vaginal trachelectomy or needle conization were performed according to tumor extent and topography. The follow-up period started once free surgical margins were reached. Results Out of 44 women enrolled, 32 women (IA2=7, IB1=23, IB2=2) successfully completed FSS. NAC was administered in 9 (28.1%) cases. A simple trachelectomy was performed in 11 patients and needle conization in 21 patients. During the follow-up, 6 out of 32 women became pregnant. Of these, 1 miscarried and 5 successfully delivered. Disease recurred in 6 patients; 5 recurrences were central and 1 recurrence presented as an ovarian mass. Invasive cervical carcinoma, high-grade squamous intraepithelial (HSIL), and low-grade squamous intraepithelial (LSIL) lesions were detected in 4, 1 and 1 patients, respectively. Three of them received NAC. All events were detected within 16months after surgery. Conclusions Nearly 27% of patients cannot complete FSS due to node positivity, progression during NAC, or involved margins. The total recurrence rate reached 18.8%, with the majority of invasive recurrences detected in patients after NAC followed by FSS. These patients represent cases at a higher risk of recurrence even if adequate free margins are reached by surgery. Nearly half of the cohort did not consider pregnancy in the near future because of personal reasons.

Einleitung: Lymphozelen stellen eine haufige Komplikation nach pelviner Lymphadenektomie bei Frauen mit gynakologischen Malignomen dar. Obwohl Lymphozelen zumeist asymptomatisch sind, kann eine Superinfektion eine medizinische oder mechanische Intervention notwendig machen. Eine unizentrische randomisiert kontrollierte Studie zeigte bereits erste Hinweise, dass ein Kollagen-Fibrin Vlies (Tachosil®) effektiv in der Pravention von asymptomatischen Lymphozelen sein konnte. Diese Studie war jedoch zu klein, um den klinisch wesentlich relevanteren Endpunkt – symptomatische Lymphozelen – zu evaluieren. Material und Methodik: Im Rahmen einer multizentrischen, verblindeten, randomisiert kontrollierten Arzneimittelgesetzstudie (Medizinische Universitat Wien, Ruhr Universitat Bochum, Charles Universitat Prag und Kliniken-Essen-Mitte) wurden 154 Frauen inkludiert, bei denen im Rahmen eines gynakologischen Malignoms (Zervix-, Endometrium- oder Ovarialkarzinom) eine pelvine Lymphadenektomie (LA) durchgefuhrt wurde. Frauen wurden intraoperativ nach durchgefuhrter pelviner LA in die Gruppe „Tachosil-Applikation“ oder „keine Tachosil-Applikation“ zugeteilt. Primarer Endpunkt war das Auftreten einer Lymphozele CTCAE v4.03 Grad > 2 innerhalb von 4 Wochen nach der Operation. Sekundarer Endpunkt war das Auftreten einer sonographisch verifizierten Lymphozele 4 Wochen nach Operation. Ergebnisse: 12/154 (7,8%) Frauen erschienen nicht zur Nachsorgeuntersuchung 4 Wochen nach der Operation. Symptomatische Lymphozelen traten insgesamt bei 9/142 (6,3%) Frauen nach pelviner LA auf. Es zeigte sich kein Unterschied in der Pravalenz der symptomatische Lymphozelen zwischen den beiden Gruppen (T: 7,9%, K: 5,1%; p = 0,5, OR 1,6 [0,4 – 6,3]). Auch in der Pravalenz der asymptomatischen Lymphozelen zeigte sich kein Unterschied zwischen den beiden Gruppen (T: 57,1%, K: 42,9%; p = 0,1, OR 1,9 [0,9 – 4,1]). Weiters zeigte sich kein Unterschied bei den schweren unerwunschten Nebenwirkungen, den intra- und postoperativen Komplikationen zwischen den beiden Gruppen. Im Rahmen einer multivariaten binaren logistischen Regression konnten keine pradiktiven Faktoren fur das Auftreten von symptomatischen Lymphozelen identifiziert werden. Diskussion: Die Applikation von Tachosil® nach pelviner Lymphadenektomie zeigte keine Wirksamkeit in der Vermeidung sowohl symptomatischer als auch asymptomatischer Lymphozelen bei Frauen mit gynakologischen Malignomen. Es konnten daruber hinaus keine pradiktiven Faktoren fur das Auftreten von symptomatischen Lymphozelen identifiziert werden.