Search

Background: The impact of adjuvant radiotherapy (RT) to the vulva with regard to prognosis and local recurrence in patients with vulvar squamous cell cancer (VSCC) is poorly described.Patients and methods: In the AGO-CaRE-1 study 1618 patients with primary VSCC FIGO stage ≥ IB, treated between 1998-2008, were documented. In this retrospective subanalysis, 360 patients were included based on the following criteria: nodal involvement (pN+), known RT treatment and known radiation fields.Results: The majority had pT1b/pT2 tumors (n=299; 83.1%). In 76.7%, R0 resection was achieved. 57/360 (15.8%) N+ patients were treated with adjuvant RT to the groins/pelvis and 146/360 (40.5%) received adjuvant RT to the vulva and groins/pelvis. 157/360 (43.6%) patients did not receive any adjuvant RT. HPV status was available in 162/360 patients (45.0%), 75/162 tumors were HPV+(46.3%), 87/162 (53.7%) HPV-. During a median follow-up of 17.2 months, recurrence at the vulva only occurred in 25.5% of patients without adjuvant RT, in 22.8% of patients with adjuvant RT to groins/pelvis and in 15.8% of patients with adjuvant RT to the vulva and groins/pelvis respectively. The risk reducing effect of local RT was independent of the resection margin status. 50% disease free survival time (50% DFST) indicated a stronger impact of adjuvant RT to the vulva in HPV+ compared to HPV- patients (50% DFST 20.7 months vs. 17.8 months).Conclusion: Adjuvant RT to the vulva was associated with a lower risk for local recurrence in N+ VSCC independent of the resection margin status. This observation was more pronounced in patients with HPV+ tumors in comparison to HPV– tumors.

Since the publication of the updated German guideline in 2015, the recommendations for performing pelvic lymphadenectomy (LAE) in patients with vulvar cancer (VSCC) have changed considerably. The guideline recommends surgical lymph node staging in all patients with a higher risk of pelvic lymph node involvement. However, the current data do not allow the population at risk to be clearly defined, therefore, the indication for pelvic lymphadenectomy is still not clear. There are currently two published German patient populations who had pelvic LAE which can be used to investigate both the prognostic effect of histologically verified pelvic lymph node metastasis and the relation between inguinal and pelvic lymph node involvement. A total of 1618 patients with primary FIGO stage ≥ IB VSCC were included in the multicenter AGO CaRE-1 study (1998 – 2008), 70 of whom underwent pelvic LAE. During a retrospective single-center evaluation carried out at the University Medical Center Hamburg-Eppendorf (UKE), a total of 514 patients with primary VSCC treated between 1996 – 2018 were evaluated, 21 of whom underwent pelvic LAE. In both cohorts, around 80% of the patients who underwent pelvic LAE were inguinally node-positive, with a median number of three affected groin lymph nodes. There were no cases of pelvic lymph node metastasis without inguinal lymph node metastasis in either of the two cohorts. Between 33 – 35% of the inguinal node-positive patients also had pelvic lymph node metastasis; the median number of affected groin lymph nodes in these patients was high (> 4), and the maximum median diameter of the largest inguinal metastasis was > 40 mm in both cohorts. Pelvic lymph node staging and pelvic radiotherapy is therefore probably not necessary for the majority of node-positive patients with VSCC, as the relevant risk of pelvic lymph node involvement was primarily found in node-positive patients with high-grade disease. More, ideally prospective data collections are necessary to validate the relation between inguinal and pelvic lymph node involvement.

Annals of surgical oncology 28(11), 6696-6704 (2021). doi:10.1245/s10434-021-09744-y, Published by Springer, Berlin [u.a.]

Purpose: This study aimed to report the uptake of hysterectomy and/or bilateral salpingo-oophorectomy (BSO) to prevent gynaecological cancers (risk-reducing surgery [RRS]) in carriers of pathogenic MMR (path_MMR) variants.Methods: The Prospective Lynch Syndrome Database (PLSD) was used to investigate RRS by a cross-sectional study in 2292 female path_MMR carriers aged 30-69 years.Results: Overall, 144, 79, and 517 carriers underwent risk-reducing hysterectomy, BSO, or both combined, respectively. Two-thirds of procedures before 50 years of age were combined hysterectomy and BSO, and 81% of all procedures included BSO. Risk-reducing hysterectomy was performed before age 50 years in 28%, 25%, 15%, and 9%, and BSO in 26%, 25%, 14% and 13% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 carriers, respectively. Before 50 years of age, 107 of 188 (57%) BSO and 126 of 204 (62%) hysterectomies were performed in women without any prior cancer, and only 5% (20/392) were performed simultaneously with colorectal cancer (CRC) surgery.Conclusion: Uptake of RRS before 50 years of age was low, and RRS was rarely undertaken in association with surgical treatment of CRC. Uptake of RRS aligned poorly with gene-and age-associated risk estimates for endometrial or ovarian cancer that were published recently from PLSD and did not correspond well with current clinical guidelines. The reasons should be clarified. Decision-making on opting for or against RRS and its timing should be better aligned with predicted risk and mortality for endometrial and ovarian cancer in Lynch syn-drome to improve outcomes. (C) 2021 The Author(s). Published by Elsevier Ltd.

Purpose To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR ( path_MMR ) variants. Methods The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. Results Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1 , path_MSH2 , path_MSH6 , and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. Conclusion Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

Despite an increasing incidence with simultaneous decreasing age of onset, vulvar squamous cell carcinoma (VSCC) is still a disease that mainly effects the elderly population. Data on the association of age with prognosis and treatment patterns in VSCC are sparse.This is an analysis of the AGO-CaRE-1 cohort. Patients with VSCC (FIGO stage ≥1B), treated at 29 cancer centers in Germany from 1998 to 2008, were included in a centralized database (n = 1618). In this subgroup analysis patients were analyzed according to age [50 yrs. (n = 220), 50-69 yrs. (n = 506), ≥70 yrs. (n = 521)] with regard to treatment patterns and prognosis. Only patients with documented age, surgical groin staging and known nodal status were included (n = 1247). Median follow-up was 27.5 months.At first diagnosis, women ≥70 yrs. presented with more advanced tumor stages (0.001), larger tumor diameter (0.001), poorer ECOG status (0.001), more frequent HPV negative tumors (p = 0.03) as well as a higher rate of nodal involvement (0.001). Disease recurrence occurred significantly more often in elderly patients (p = 0.001) and age as well as ECOG status, microscopic residual resection, tumor stage, grading, and (chemo)radiation were independent prognostic factors for death or recurrence in multivariate analysis. 2-year disease-free survival rates were 59.3% (≥70 yrs), 65.8% (50-69 yrs) and 81.1% (50 yrs), respectively (p 0.001).Older women with VSCC present with advanced tumor stages at first diagnosis and have an increased risk of recurrence as well as a decreased 2-year DFS in comparison to younger patients. Potential reasons could be self-awareness and/or more aggressive tumor biology due to HPV independent disease.

Cervical malignancy is triggered by human papillomavirus infection but the risk for cervical cancer has a hereditary component. From a recent Genome Wide Association Study meta‐analysis, 2q14.1 (PAX8) and 6p21.32 (PBX2) have been proposed as novel cervical cancer susceptibility loci. We investigated the two main signals at these loci in an independent case‐control series of 2578 cases with cervical dysplasia or carcinoma and 1483 healthy females. We find significant associations for both variants, rs10175462 at PAX8 and rs2856437 at PBX2, with overall cervical disease (rs10175462: odds ratio [OR] 0.82, 95% confidence interval [CI] 0.74‐0.91, P = 2.4 × 10−4; rs2856437: OR 1.52, 95% CI 1.14‐2.02, P = .004). Both variants showed evidence of association with invasive squamous cervical cancer (rs10175462: OR 0.80, 95% CI 0.68‐0.94, P = .006; rs2856437: OR 1.56, 95% CI 1.03‐2.36, P = .036) and with high‐grade dysplasia (rs10175462: OR 0.79, 95%CI 0.70‐0.90, P = 1.9 × 10−4; rs2856437: OR 1.58, 95% CI 1.15‐2.17, P = .005). A combined analysis of high‐grade dysplasia and invasive cervical cancer also showed significant associations for both variants (rs10175462: OR 0.81, 95% CI 0.73‐0.91, P = 2.4 × 10−4; rs2856437: OR 1.57, 95% CI 1.18‐2.10, P = .002). No association was detected for rs2856437 with low‐grade dysplasia, while rs10175462 showed weak evidence of association (P = .05). RNA analyses in cervical samples revealed that PAX8 transcripts were upregulated in HPV‐positive lesions (P = .008) but this was not observed in the presence of the protective minor allele of rs10175462. The rs10175462 genotype also correlated with reduced levels of the lncRNA PAX8‐AS1 (P

Introduction Gynaecological sarcomas are rare and there is very limited evidence about symptoms at primary diagnosis. Most knowledge is based on retrospective analysis. Methods We present data of 410 patients (pts) in the primary situation. Overall, 87.91% of pts had documented symptom data, which were analysed descriptively. A distinction was made between pre- (prem., ≤52 yrs) and postmenopausal (postm., >52 yrs.). Results The average age of pts was 56 yrs (range 15–88 yrs). Leiomyosarcoma (LMS) was diagnosed in 44.7%, endometrial stromal sarcoma (ESS) in 26.6% (62.6% low grade (LG-ESS) and 37.4% high grade (HG-ESS)). Undifferentiated sarcoma (US) and adenosarcoma (AS) were observed in 5.7% and 8.7% respectively. In prem. and postm. pts with LMS, the leading symptom (LS) was abdominal pain (ap) in 34.4%. and 39.5% respectively. In prem. HG-ESS the LS were ap and bleeding disorders (bd) in both 33.3%. In postm. HG-ESS and prem. LG-ESS the LS was vaginal bleeding (vb) in 29% and 33.3% respectively. In prem. AS the LS was ap in 27.3%, whereas in postm. AS it was postmenopausal bleeding (pb) in 29.2%. In prem. US the LS were bd and vb both at 66.7%. In postm. US the LS was ap in 47.4%. Conclusions We analyzed the LS of different histopathological subtypes in primary gynaecological sarcoma for the first time. Bleeding disorders and abdominal pain are the main symptoms in all subtypes. Symptoms are heterogeneous and about every 5th woman reported unspecific symptoms. This underlines the importance of awareness for gynaecological sarcoma.

Background:\ud State-of-the art therapy for recurrent ovarian cancer suitable for platinum-based re-treatment includes bevacizumab-containing combinations (eg, bevacizumab combined with carboplatin–paclitaxel or carboplatin–gemcitabine) or the most active non-bevacizumab regimen: carboplatin–pegylated liposomal doxorubicin. The aim of this head-to-head trial was to compare a standard bevacizumab-containing regimen versus carboplatin–pegylated liposomal doxorubicin combined with bevacizumab.\ud Methods:\ud This multicentre, open-label, randomised, phase 3 trial, was done in 159 academic centres in Germany, France, Australia, Austria, and the UK. Eligible patients (aged ≥18 years) had histologically confirmed epithelial ovarian, primary peritoneal, or fallopian tube carcinoma with first disease recurrence more than 6 months after first-line platinum-based chemotherapy, and an Eastern Cooperative Oncology Group performance status of 0–2. Patients were stratified by platinum-free interval, residual tumour, previous antiangiogenic therapy, and study group language, and were centrally randomly assigned 1:1 using randomly permuted blocks of size two, four, or six to receive six intravenous cycles of bevacizumab (15 mg/kg, day 1) plus carboplatin (area under the concentration curve [AUC] 4, day 1) plus gemcitabine (1000 mg/m 2, days 1 and 8) every 3 weeks or six cycles of bevacizumab (10 mg/kg, days 1 and 15) plus carboplatin (AUC 5, day 1) plus pegylated liposomal doxorubicin (30 mg/m 2, day 1) every 4 weeks, both followed by maintenance bevacizumab (15 mg/kg every 3 weeks in both groups) until disease progression or unacceptable toxicity. There was no masking in this open-label trial. The primary endpoint was investigator-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1. Efficacy data were analysed in the intention-to-treat population. Safety was analysed in all patients who received at least one dose of study drug. This completed study is registered with ClinicalTrials.gov, NCT01837251.\ud Findings:\ud Between Aug 1, 2013, and July 31, 2015, 682 eligible patients were enrolled, of whom 345 were randomly assigned to receive carboplatin–pegylated liposomal doxorubicin–bevacizumab (experimental group) and 337 were randomly assigned to receive carboplatin–gemcitabine–bevacizumab (standard group). Median follow-up for progression-free survival at data cutoff (July 10, 2018) was 12·4 months (IQR 8·3–21·7) in the experimental group and 11·3 months (8·0–18·4) in the standard group. Median progression-free survival was 13·3 months (95% CI 11·7–14·2) in the experimental group versus 11·6 months (11·0–12·7) in the standard group (hazard ratio 0·81, 95% CI 0·68–0·96; p=0·012). The most common grade 3 or 4 adverse events were hypertension (88 [27%] of 332 patients in the experimental group vs 67 [20%] of 329 patients in the standard group) and neutropenia (40 [12%] vs 73 [22%]). Serious adverse events occurred in 33 (10%) of 332 patients in the experimental group and 28 (9%) of 329 in the standard group. Treatment-related deaths occurred in one patient in the experimental group (

The human leukocyte antigen (HLA) locus on chromosome 6 has been reported to be associated with cervical cancer. We investigated two independent single-nucleotide polymorphisms in a large case-control series of cervical dysplasia and carcinoma that has been newly established by the German Cervigen Consortium, comprising a total of 2481 cases and 1556 healthy females. We find significant associations for both variants, rs9272117 at HLA-DQA1 and rs2844511 at MICA and HCP5, with cervical disease. Both variants showed evidence of association with invasive cervical cancer (rs9272117: OR 0.89, 95% CI 0.79-0.99, P = .036; rs2844511: OR 1.17, 95% CI 1.04-1.31, P = .008) and with high-grade dysplasia (rs9272117: OR 0.78, 95% CI 0.70-0.87, P = 7.1 × 10-6 ; rs2844511: OR 1.13, 95% CI 1.01-1.26, P = .035), as well as in a combined analysis of both groups (rs9272117: OR 0.83, 95% CI 0.75-0.91, P = 6.9 × 10-5 ; rs2844511: OR 1.14, 95% CI 1.04-1.26, P = .005). Variant rs2844511, but not rs9272117, also showed modest evidence of association with low-grade dysplasia (OR 1.26, 95% CI 1.04-1.54, P = .019). In case-only analyses, rs2844511 tended to predict HPV status (P = .044) and rs9272117 tended to associate with HPV16 (P = .022). RNA studies in cervical samples showed a significant correlation in the transcript levels of MICA, HCP5 and HLA-DQA1, suggesting extensive co-regulation. All three genes were upregulated in HPV16-positive samples. In stratified analyses, rs9272117 was associated with HLA-DQA1 levels, specifically in HPV-positive samples, while rs2844511 was associated with MICA and HCP5 levels. The risk allele of rs2844511 was required for correlations between MICA or HCP5 with HLA-DQA1. Altogether, our results support 6p21.32-33 as the first consistent cervical cancer susceptibility locus and provide evidence for a link between genetic risk variants, HPV16 status and transcript levels of HLA-DQA1, HCP5 and MICA, which may contribute to tumor immune evasion.

Introduction/Background Obesity is associated with decrased survival in several cancer entities. The influence of obesity on prognosis of vulvar cancer patients is not clear. However, knowledge about this may have consequences on treatment and follow-up. Methodology This is an analysis of the large AGO-CaRE-1 study which included vulvar cancer patients (UICC stage IB and higher), treated in 29 cancer centers between 1998 and 2008, in order to analyze treatment patterns and prognostic factors. Results In total, 849 eligible patients were divided into two groups depending on their body mass index (BMI, 0.05). Radical vulvectomies were performed more frequently in patients having a BMI ≥30 kg/m² (61.1% vs. 51.8%, p=0.042). Interestingly, we detected a higher recurrence rate in the group having a BMI ≥30 kg/m² (43.4%, vs. 28.3%, p Noteworthy, this association was not linear: in an additional subgroup analysis on five BMI groups we detected a longer time to recurrence in women with a slightly increased BMI 25–30 kg/m² compared to those with a normal BMI between 19 and 25 kg/m² (OR 0.55, 95%CI 0.33–0.91, p=0.02). Conclusion In this first large study about the association between obesity and prognosis of vulvar cancer patients, we observed that a BMI ≥30 kg/m² was associated with shorter DFS, mainly attributed to a higher risk for local recurrence. Disclosure Conflicts of Interest and Source of Funding: All authors declare that there are no conflicts of interest involved with the presented data. The CaRE-1 study was supported by medac oncology without restriction in protocol or analysis

Background: There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma—a human papillomavirus–dependent pathway characterized by p16 overexpression and a human papillomavirus–independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed.Objective: The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance.Study Design: The Arbeitsgemeinschaft Gynaecological Oncology Chemo and Radiotherapy in Epithelial Vulvar Cancer-1 study is a retrospective cohort study of 1618 patients with primary vulvar squamous cell carcinoma Fédération Internationale de Gynécologie et d'Obstétrique stage ≥1B treated at 29 gynecologic cancer centers in Germany between 1998 and 2008. For this translational substudy, formalin-fixed paraffin-embedded tissue was collected. A tissue microarray was constructed (n=652 samples); p16 and p53 expression was determined by immunohistochemistry. Human papillomavirus status and subtype were analyzed by polymerase chain reaction.Results: p16 immunohistochemistry was positive in 166 of 550 tumors (30.2%); p53 staining in 187 of 597 tumors (31.3%). Only tumors with available information regarding p16 and p53 immunohistochemistry and without p53 silent expression pattern were further analyzed (n=411); 3 groups were defined: p53+ (n=163), p16+/p53− (n=132), and p16−/p53− (n=116). Human papillomavirus DNA was detected in 85.6% of p16+/p53− tumors; human papillomavirus-16 was the most common subtype (86.3%). Patients with p16+ tumors were younger (64 vs 72 years for p53+, respectively, 69 years for p16−/p53− tumors; PConclusion: p16 overexpression is associated with an improved prognosis whereas p53 positivity is linked to an adverse outcome. Our data support the hypothesis of a clinically relevant third subgroup of vulvar squamous cell carcinoma with a p53−/p16− phenotype showing an intermediate prognosis that needs to be further characterized.

6090 Background: Despite an increasing incidence with simultaneous decreasing age of onset, the impact of age on prognosis and treatment patterns in primary squamous cell vulvar cancer (VSCC) has not extensively been studied yet. Methods: This is a subgroup analysis of the AGO-CaRE-1 study. Patients (pts) with VSCC (FIGO stage ≥1B), treated at 29 cancer centers in Germany from 1998-2008, were included in a centralized database (n = 1618). In this subgroup analysis pts were analyzed according to age ( < 50yrs (n = 220), 50–69yrs (n = 506), ≥70yrs (n = 521)) with regard to treatment patterns and prognosis. Only pts with documented age, surgical groin staging and known nodal status were included (n = 1247). Median follow-up was 27.5 months. Results: At first diagnosis, women ≥70yrs presented with more advanced tumor stages ( < 0.001), larger tumor diameter ( < 0.001), poorer ECOG status ( < 0.001), higher tumor grading (0.048), as well as a higher rate of nodal involvement ( < 0.001). Older women ≥70yrs showed more commonly HPV negative tumors compared to the other age groups (54% vs. 36.5% in < 50yrs vs. 47.9% in 50-69yrs, p = 0.03). Disease recurrence occurred significantly more often in elderly women (48% vs. 21% in < 50yrs vs. 37.4% in 50-69yrs, p = 0.001). Particularly isolated vulvar recurrence was more frequent in the elderly in comparison to the younger groups (18.2% vs. 15.2% in 50-69yrs vs. 12.7% in < 50yrs, p = 0.001). Age was an independent prognostic factor for disease-free survival (DFS) (HR: 1.7, 95%CI: 1.24-2.46, p = 0.001) with 2-year DFS being 81.1% (< 50yrs), 65.8% (50–69yrs), and 59.3% (≥70yrs), respectively. Elderly women (age group ≥70) had a 221% higher risk for death or recurrence, compared to the youngest group (HR: 3.21, p < 0.001). In a multivariate analysis ECOG, tumor stage, grading, and receipt of (chemo)radiation were further independent prognostic factors for recurrence. Conclusions: Older women with VSCC present with advanced tumor stages at first diagnosis and have an increased risk of recurrence as well as a decreased 2-year PFS in comparison to younger pts groups. Potential reasons for delayed time of diagnosis could be self-awareness and/or more aggressive tumor biology due to HPV negative disease.

Lymph node ratio (LNR) can predict treatment outcome and prognosis in patients with solid tumors. Aim of the present analysis was to confirm the concept of using LNR for assessing outcome in patients with vulvar cancer after surgery with inguinal lymphadenectomy in a large multicenter project.The AGO-CaRE-1 study multicenter database was used for analysis. LNR was defined as ratio of number of positive lymph nodes (LN) to the number of resected. Previously established LNR risk groups were used to stratify patients. LNR was investigated with respect to clinical parameters. Univariate and multivariable survival analyses were performed to assess the value of LNR in order to predict overall (OS) and progression-free (PFS) survival.In total, 1047 patients treated with surgery including inguinal lymph node resection for squamous cell carcinoma of the vulva were identified from the database. Of these, 370 (35.3%) were found to have positive inguinal LN. In total, 677 (64.7%) had a LNR of 0% (N0), 255 (24.4%) a LNR of0% 20%, and 115 (11%) a LNR of ≥20%. Patients with higher LNR were found to have larger tumor size (P .001), advanced tumor stage (P .001), high tumor grade (P .001), and deep stromal invasion (P .001), more frequently. Three-year PFS rates were 75.7%, 44.2%, and 23.1% and three-year OS rates were 89.7%, 65.4%, and 41.9%, in patients with LNRs 0%,0% 20%, and ≥20%, respectively (P .001, P .001). On multivariable analyses LNR (HR 7.75, 95%-CI 4.01-14.98, P .001), FIGO stage (HR 1.41, 95%-CI 1.18-1.69, P .001), and patient's performance status (HR 1.59, 95%-CI 1.39-1.82, P .001), were associated with PFS. In addition, LNR (HR 12.74, 95%-CI 5.64-28.78, P .001), and performance status (HR 1.72, 95%-CI 1.44-2.07, P .001) were also the only two parameters independently associated with OS. LNR generally showed stronger correlation than number of affected LN when comparing the two different multivariable models.In women with vulvar cancer LNR appears to be a consistent, independent prognostic parameter for both PFS and OS and allows patient stratification into three distinct risk groups. In survival analyses, LNR outperformed nodal status and number of positive nodes.

Borderline tumors of the ovary (BOT) represent an entity of ovarian neoplasms with low malignant potential and excellent prognosis. Mainstay of therapy is surgery including adequate staging and complete tumor resection, possibly inducing long-term side effects, especially in premenopausal women. The aim of this study was to evaluate quality of life (QoL) and sexual function in patients treated for BOT, also with respect to treatment modalities.This prospective study was part of an ambidirectional multicentric cohort study in patients with BOT in Germany. Patients from seven centers completed three questionnaires after completion of therapy. QoL and sexual function data were correlated with treatment characteristics: surgical approach, lymphadenectomy, and fertility sparing surgery.One hundred ten patients returned the questionnaires. Median follow-up was 4.0 years. The majority lived in a relationship (n = 85, 77%, missing n = 4), and 49% (n = 54, missing n = 6) were sexually active. The main reason for sexual inactivity was "no partner" (38%). The women had a mean global health status of 69.8 (SD 22.7; min 0, max 100), with 100 implying perfect health. Mean QoL score was 73.7 (SD 23.3, range 0 to 100). Both scores showed no difference regarding fertility preserving surgery, surgical approach, and lymphadenectomy. Sexually active women had a significantly higher QoL (78.7 vs. 67.4, p = 0.0156) and global health status (75.9 vs. 60.9, p = 0.0013) than inactive patients.In this prospective study, patients who had been diagnosed with BOT had a very good quality of life and global health status. Sexually inactive women stated lack of a partner as the main reason and had an inferior HRQoL compared to sexually active women.

e17130 Background: Obesity is associated with worse patients’ survival in several cancer entities. Vulvar cancer as well as obesity show increasing incidence over the last years. The influence of obesity on prognosis of vulvar cancer patients is not clear. However, knowledge about this may have consequences on prevention, treatment, and follow-up. Methods: This is an analysis of the large AGO-CaRE-1 study. Patients suffering from squamous cell vulvar cancer (UICC stage IB and higher), treated in 29 cancer centers between 1998 and 2008, were categorized in a database, in order to analyze treatment patterns and prognostic factors in a retrospective setting. Results: In total, 849 patients with documented height and weight were divided into two groups depending on their body mass index (BMI, < 30 vs. ≥30 kg/m²). There was no difference in the baseline variables (age, tumor diameter, depth of infiltration, tumor stage, nodal invasion, tumor grade) between both groups (p > 0.05). However, we identified differences regarding ECOG status and preexistent comorbidities (cardiovascular, dementia) towards healthier patients with BMI < 30 kg/m². Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ (p > 0.05). Patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1 % vs. 51.8%, p = 0.042). During follow-up, there was a higher recurrence rate in the group having a BMI ≥30 kg/m² (43.4%, vs. 28.3%, p < 0.01) due to an increased rate of local recurrences (33.3% vs. 18.5%, p < 0.01). The rate of groin and distant recurrences was similar between both groups (p > 0.05). Noteworthy, we observed a significantly shorter disease free survival (DSF) of the obese patients in univariate analysis (HR 1.362, 95%CI 1.093-1.696, p = 0.006). Even in multivariate Cox-regression analysis including age, ECOG, tumor stage, type of surgery, nodal invasion, tumor grade, and comorbidities patients with BMI ≥30 kg/m² had a significantly shorter DFS (HR 1.811, 95%CI 1.005-3.262, p = 0.048). Conclusions: In this first large study about the association between obesity and prognosis of vulvar cancer patients, we observed that a BMI ≥30kg/m² was associated with shorter DFS, mainly attributed to a higher risk for local recurrence.

5592 Background: Currently, there are two major pathways for tumorigenesis of vulvar squamous cell carcinoma (VSCC) – an HPV-dependent with p16 overexpression as a surrogate for HPV-associated transformation and an HPV-independent route linked to lichen sclerosus, characterized by p53 mutation. A possible correlation of HPV dependency with a favourable prognosis has been proposed. Methods: The AGO CaRE-1 study is a retrospective survey of pts with primary VSCC FIGO stage ≥1B (UICC-TNM version 6) treated at 29 gynecologic cancer centers in Germany 1998-2008 (n = 1,618). For this CaRE-translational sub-study available FFPE tissue was collected centrally (n = 648). A tissue micro array (TMA) was constructed; p16 and p53 expression was determined by immunohistochemistry (IHC). HPV status and subtype were analyzed by PCR. Results: p16 IHC was interpretable in 550 TMA spots and considered positive in 166/550 (30.2%). HPV DNA was detected in 78.4% of the p16+ tumors, with HPV 16 being the most common subtype (88.3%) . Pts with p16+ tumors were younger at diagnosis (63 vs. 70 yrs for p16- tumors; p = 0 < 0.01) and showed lower rates of lymph-node involvement (29.0% vs. 39.7%; p = 0.021). p53 IHC was interpretable in 597 spots, 187/597 (31.3%) were considered positive. Pts with p53+ tumors were older at first diagnosis (71 vs. 66 yrs; p = 0.001 for p53- tumors) and showed lymph-node involvement more often (43.3% vs. 31.1%; p = 0.007). There was a relevant number of tumors with neither p16 nor p53 overexpression (221/535); while co-expression of p53 and p16 was rare (12/535). For survival analyses, three groups were defined: p53+ (n = 163), p16+/p53- (n = 151) and p16-/p53- (n = 221). 2-y-disease-free (DFS) and overall survival (OS) rates were significantly different between the groups: DFS: p53+ 47.0%; p16-/p53- 53% and p16+/p53- 65.5% (p < 0.001); OS: 70.4%, 72.6% and 82.7% (p = 0.003), respectively. Adjustment for age and nodal status showed consistent p16 and p53 effects regarding DFS. Conclusions: p16 overexpression is associated with an improved prognosis in VSCC while p53 positivity is linked to an adverse outcome. Our data provide evidence of a clinically relevant third subgroup of VSCC with a p53-/p16- phenotype showing an intermediate prognosis that needs to be further characterized.

Aims: The value of ECG in the perioperative risk stratification under modern treatment options is uncertain. The main objective of the present analysis was to determine the usefulness of a pre-operative ECG derivation for evaluating the risk of perioperative morbidity and mortality. Methods: We performed a secondary analysis of the prospective, international, multicenter, observational “No-Risk” Study (N-terminal B-type natriuretic peptide [NT-proBNP] for the assessment of the perioperative cardiac risk after major noncardiac surgery) to determine the prognostic value of 12-lead ECG. Inclusion criteria were age >55 years and at least one of the following cardiovascular risk factors: arterial hypertension, diabetes mellitus, dyslipidemia, active smoking, and family history positive for coronary heart disease. The combined primary endpoint included total mortality, acute myocardial infarction (NSTEMI and STEMI), cardiopulmonary resuscitation, heart failure, and asystole or ventricular fibrillation during hospitalization. ECGs from 616 patients enrolled from 2006 to 2009 prior to noncardiac surgery in the No-Risk Study were analyzed. Results: The mean age was 67.6 (±8.1) years; 300 (48.7%) patients were male. Fourteen (2.3%) patients suffered from the combined primary endpoint while in the hospital. In Kaplan-Meier analyses, a pathologic Q wave and QTc > 500 ms were significantly related to the incidence of the primary endpoint (p < 0.001, p = 0.042, respectively), whereas other ECG parameters such as LBBB, RBBB, PQ interval, QRS interval, and others were not related to worse in-hospital outcome. Conclusion: The 12-lead ECG is still an important diagnostic tool for perioperative risk assessment of cardiovascular events in noncardiac surgery in patients at risk.

Objectives The aim of this study is to evaluate the activity and toxicity of fulvestrant, a pure estrogen receptor antagonist in patients with advanced or recurrent endometrial cancer, expressing estrogen and/or progesterone receptors (ER/PR). Methods Eligible patients with advanced or recurrent endometrial cancer not amenable to curative surgery and/or radiotherapy were treated with fulvestrant at a dose of 250mg by IM injection every 4weeks for at least 12weeks. Therapy was continued until disease progression, death, intolerable side effects or end of study. Response was assessed in patients with at least one target lesion according to WHO-criteria. Results Thirty-five patients were enrolled in this study and received at least one injection of fulvestrant (intention to treat-population, ITT). Twenty six patients received the intended 3 injections of fulvestrant (per protocol population, PP). There was no complete response but 4 partial responses (11.4% ITT) and 8 stable diseases. The median time to progression was 2.3months (ITT). Overall survival was 13.2months (ITT). Treatment was well tolerated. Conclusions Fulvestrant at a dose of 250mg IM every 4weeks has marginal activity and good tolerability in patients with ER and/or PR positive advanced or recurrent endometrial cancer. A loading dose strategy and the use of 500mg/4weeks might improve the efficacy of this treatment.

Background Borderline ovarian tumours (BOTs) are recognised as a unique entity of ovarian tumours that do not exert infiltrative destructive growth or stromal invasion. Prognosis of BOT is much better compared to the more common invasive epithelial ovarian cancer. Information regarding prognostic factors is inconclusive and no prospective studies exist that evaluate therapeutic strategies. We therefore started a retrospective–prospective cohort study to better understand BOT and identify scenarios in which future studies could be developed. Methods Consecutive patients with BOT treated between 1998 and 2008 in 24 German centres were analysed. The retrospective part of the study retrieved patients’ data from hospital records and clinical tumour registries while active follow-up and an independent central pathology review were carried out prospectively. Findings BOT was confirmed in 950 patients, two thirds had serous BOT and 30.5% mucinous BOT. Most were diagnosed in stage I (82.3%); 7.6% and 10.1% had stages II and III, respectively. Overall, 74 patients (7.8%) experienced relapse and 43 (4.5%) died within the observation period. Multivariate analysis revealed higher stage, incomplete staging, tumour residuals, and organ preservation as independent prognostic factors for disease recurrence. Neither microinvasion nor micropapillary growth pattern showed any significant impact. Of 74 relapsed patients, 30% had malignant transformation to invasive ovarian cancer with five-year progression-free survival and overall survival of 12% and 50%, respectively. Interpretation Prognosis of BOT correlates with tumour-related as well as surgery-related factors. The balance between recurrence risk and organ preservation and fertility-sparing surgery is an important issue deserving further research.

Analyzing the large patient cohort of the multicenter AGO-CaRE-1 study, we compared isolated sentinel lymph node dissection (SLND) with radical lymph node dissection (LND) of the groin in relation to recurrence rates and survival.The AGO-CaRE-1 study retrospectively collected data on treatment patterns and follow-up of vulvar cancer patients [International Federation of Gynecology and Obstetrics (FIGO) stage ≥1B] treated at 29 gynecologic cancer centers between 1998 and 2008. This subgroup analysis evaluated the influence of SLND alone on progression-free survival (PFS) and overall survival (OS).In 487 (63.1%) of 772 included patients with tumors smaller than 4 cm, an LND was performed and no metastatic lymph nodes were detected (LN0). Another 69/772 (8.9%) women underwent SLND alone, showing a negative SLN (SLN0). Tumors in the LN0 group were larger and showed a deeper invasion (LN0 vs. SLN0 tumor diameter: 20.0 vs. 13.0 mm, p 0.001; depth of invasion: 4.0 vs. 3.0 mm, p = 0.002). After a median follow-up of 33 months (0-156), no significant differences in relation to isolated groin recurrence rates (SLN0 3.0% vs. LN0 3.4%, p = 0.845) were detected. Similarly, univariate 3-year PFS analysis showed no significant differences between both groups (SLN0 82.7% vs. LN0 77.6%, p = 0.230). A multivariate Cox regression analysis, including tumor diameter, depth of invasion, age, grading, and lymphovascular space invasion was performed: PFS [hazard ratio (HR) 0.970, 95% confidence interval (CI) 0.517-1.821] and OS (HR 0.695, 95% CI 0.261-1.849) did not differ significantly between both cohorts.This subgroup analysis of the large AGO-CaRE-1 study showed similar results for groin LND and SLND alone with regard to recurrence rates and survival in node-negative patients with tumors4 cm.

Aim of the study: A tumour-free pathological resection margin of >= 8 mm is considered state-of-the-art. Available evidence is based on heterogeneous cohorts. This study was designed to clarify the relevance of the resection margin for loco-regional control in vulvar cancer.Methods: AGO-CaRE-1 is a large retrospective study. Patients (n = 1618) with vulvar cancer >= FIGO stage IB treated at 29 German gynecologic-cancer-centres 1998-2008 were included. This subgroup analysis focuses on solely surgically treated node-negative patients with complete tumour resection (n = 289).Results: Of the 289 analysed patients, 141 (48.8%) had pT1b, 140 (48.4%) pT2 and 8 (2.8%) pT3 tumours. One hundred twenty-five (43.3%) underwent complete vulvectomy, 127 (43.9%) partial vulvectomy and 37 (12.8%) radical local excision. The median minimal resection margin was 5 mm (1 mm-33 mm); all patients received groin staging, in 86.5% with full dissection. Median follow-up was 35.1 months. 46 (15.9%) patients developed recurrence, thereof 34 (11.8%) at the vulva, after a median of 18.3 months. Vulvar recurrence rates were 12.6% in patients with a margin = 8 mm. When analysed as a continuous variable, the margin distance had no statistically significant impact on local recurrence (HR per mm increase: 0.930, 95% CI: 0.849-1.020; p=0.125). Multivariate analyses did also not reveal a significant association between the margin and local recurrence neither when analysed as continuous variable nor categorically based on the 8 mm cutoff. Results were consistent when looking at disease-free-survival and time-to-recurrence at any site (HR per mm increase: 0.949, 95% CI: 0.864-1.041; p = 0.267).Conclusions: The need for a minimal margin of 8 mm could not be confirmed in the large and homogeneous node-negative cohort of the AGO-CaRE database. (C) 2016 Elsevier Ltd. All rights reserved.

Background: This phase 2 trial was designed to evaluate the efficacy and toxicity of a combination of docetaxel, gemcitabine, and oxaliplatin for platinum- and paclitaxel-pretreated epithelial ovarian cancer. Patients and Methods: Heavily pretreated patients (N = 30; median age, 61 years) received docetaxel, 55 mg/m2; gemcitabine, 500 mg/m2 (day 1); and oxaliplatin, 70 mg/m2 (day 2) biweekly. Twelve patients had platinum-sensitive disease, and 18 patients had platinum-resistant disease. Results: Median follow-up was 18.6 months. No differences in patient characteristics were observed between patients with carboplatinum-sensitive and carboplatinum-resistant disease. In patients with carboplatin-sensitive disease, an overall response (OR) of 83.3%, a progression-free survival of 10.6 months, and an overall survival of 18.9 months were observed. In patients with carboplatinum-resistant disease, an OR was seen in 38.9% with a progression-free survival of 5.3 months and an overall survival of 16.3 months. Patients with platinum-refractory disease (progression under previous carboplatinum therapy, n = 13) had an OR of 23%, whereas patients with objective response but relapse less than 6 months after carboplatinum therapy had an OR of 80.0%. Grade 3 and 4 toxicities were only observed for anemia (6.7%), neutropenia (20.0%), thrombopenia, peripheral neuropathy, and diarrhea (16.7%). No neutropenic fever or treatment-related death occurred. Conclusions: In comparison with current standard protocols, a combination of docetaxel, gemcitabine, and oxaliplatin showed considerably higher efficacy without remarkable increased toxicity; particularly for patients with early relapse after a platinum-containing therapy.

Pegylated liposomal doxorubicin (PLD) is active in recurrent platinum-refractory ovarian and peritoneal cancer as demonstrated in a prospective-randomized trial. Dose-limiting toxicity in the US Food and Drug Administration-approved application schedule of PLD (50 mg/m2 every 4 weeks) was serious palmar-plantar erythrodysaesthesia (PPE). This phase II trial was aimed at reduction of the frequency of serious PPE without loss of efficacy by modifying both the application schedule and the total dose of PLD administered as palliative single-agent chemotherapy. Fifty patients were enrolled into this phase II trial. PLD was given via 30-min intravenous infusion at a dose of 20 mg/m2 every 2 weeks. Primary endpoint of the trial was the best response to chemotherapy. Secondary goals were progression-free survival, overall survival, and toxicity. Four complete responses and 16 partial responses were found resulting in an overall best response rate of 40.0%. The median progression-free survival in the intention-to-treat-population was 4.1 months [95% confidence interval (CI), 2.8-5.4 months], whereas the overall survival was 16.5 months (95% CI, 12.3-20.7 months). Although 17 (34.0%) patients developed some PPE, only one progressed to grade 3 (NCI-CTC version 2.0; 1998). No grade 4 toxicity occurred. PLD 20 mg/m2 biweekly is highly active in patients with recurrent platinum-refractory ovarian and peritoneal cancer. The frequency of grade 3 and grade 4 PPE was remarkably reduced in this trial, as compared with the frequency of serious PPE observed in patients who were administered the dose schedule of 50 mg/m2 every 4 weeks.

Patients with cervical cancer frequently suffer from anemia. This two-stage, adaptive-design study investigated the effect of anemia correction with epoetin beta on treatment outcomes. Patients with stage IIB–IVA cervical cancer received radiochemotherapy (RCT) and were randomized to epoetin 150 IU/kg three times weekly (n = 34) or standard care (control; n = 40) for up to 12 weeks. Primary end point for stage 1 aimed to establish a correlation between anemia correction and treatment failure (no complete response or relapsing within 6 months after RCT initiation) as a proof of concept before moving into stage 2. Secondary end points included progression/relapse-free survival, overall survival, response to RCT, hemoglobin (Hb) response, and safety. Median baseline Hb was 11.4 and 11.6 g/dL in epoetin and control groups, respectively. At treatment end point, median Hb increased by 1.3 g/dL with epoetin, but decreased by 0.7 g/dL in the control group (P < 0.0001). No significant correlation between Hb increase and treatment failure was demonstrated. There were no significant differences between epoetin and control groups in progression/relapse-free survival (29.4% vs 32.5% patients with events; P = 0.96), overall survival (23.5% vs 12.5% patients with events; P = 0.22) or overall complete response (53% vs 58%; P = 0.86). Adverse events were well matched between groups. This study shows that epoetin beta rapidly, effectively, and safely increases Hb levels in patients with cervical cancer receiving RCT. No positive correlation of Hb increase and improvement in clinical outcomes could be demonstrated.

Objective. Docetaxel and carboplatin are active in relapsed ovarian, peritoneal and tubal cancer. Recently, two prospective-randomized trials showed an advantage of carboplatin combination regimen with paclitaxel or gemcitabine over carboplatinum alone in platinum-sensitive cases. The question on the most effective combination with the best tolerable side effects still needs to be answered. Methods. Eligible patients had recurrent ovarian, peritoneal or tubal cancer (platinum-free interval >6 months), performance status 0–2 and normal bone marrow, renal and hepatic function. 25 patients (age 18–75 years) were enrolled into this phase II trial. Patients with debulking operation of recurrence were excluded from this study. Docetaxel 75 mg/m2 via 30-min infusion was given on day 1 followed by carboplatin (area under curve [AUC] 5) on day 1. The administration was repeated every 3 weeks over 6 courses. Primary endpoint of this trial was the response rate; secondary endpoints were progression-free survival, overall survival and toxicity. Results. In the intent-to-treat population, there were 16 (64.0%) complete and 2 (8.0%) partial responses resulting in an overall response rate of 72.0%. Three patients (12.0%) showed a stable disease and other 2 patients (8.0%) a progression of cancer. Two patients (8.0%) were not evaluable for response. Neutropenia was the most frequent G3/G4 hematologic toxicity in 15/25 patients (60.0%); but no neutropenic fever occurred in this trial. Diarrhea G3 was the most frequent G3/G4 non-hematologic toxicity in only 3/25 patients (12.0%). Dose-limiting toxicities were hypersensitivity reaction in one and depressive mood alteration requiring therapy in another case. Conclusion. Carboplatin in combination with docetaxel is highly active and well tolerated in patients with recurrent platinum-sensitive ovarian, peritoneal and tubal cancer. Prospective-randomized trials comparing this with other carboplatin therapeutic doublets in patients with recurrent ovarian cancer are a possible option for the future to answer the question on the best combination regimen.

Background: Women with node-positive vulvar cancer have a high risk for disease recurrence. Indication criteria for adjuvant radiotherapy are controversial. This study was designed to further understand the role of adjuvant therapy in node-positive disease. Methods: Patients with primary squamous-cell vulvar cancer treated at 29 gynecologic cancer centers in Germany from 1998 through 2008 were included in this retrospective exploratory multicenter cohort study. Of 1618 documented patients, 1249 had surgical groin staging and known lymph node status and were further analyzed. All statistical tests were two-sided. Results: Four hundred forty-seven of 1249 patients (35.8%) had lymph node metastases (N+). The majority of N+ patients had one (172 [38.5%]) or two (102 [22.8%]) positive nodes. The three-year progression-free survival (PFS) rate of N+ patients was 35.2%, and the overall survival (OS) rate 56.2% compared with 75.2% and 90.2% in node-negative patients (N-). Two hundred forty-four (54.6%) N+ patients had adjuvant therapy, of which 183 (40.9%) had radiotherapy directed at the groins (+/-other fields). Three-year PFS and OS rates in these patients were better compared with N+ patients without adjuvant treatment (PFS: 39.6% vs 25.9%, hazard ratio [HR] = 0.67, 95% confidence interval [CI[= 0.51 to 0.88, P = .004; OS: 57.7% vs 51.4%, HR = 0.79, 95% CI = 0.56 to 1.11, P = .17). This effect was statistically significant in multivariable analysis adjusted for age, Eastern Cooperative Oncology Group, Union internationale contre le cancer stage, grade, invasion depth, and number of positive nodes (PFS: HR = 0.58, 95% CI = 0.43 to 0.78, P < .001; OS: HR = 0.63, 95% CI = 0.43 to 0.91, P = .01). Conclusion: This large multicenter study in vulvar cancer observed that adjuvant radiotherapy was associated with improved prognosis in node-positive patients and will hopefully help to overcome concerns regarding adjuvant treatment. However, outcome after adjuvant radiotherapy remains poor compared with node-negative patients. Adjuvant chemoradiation could be a possible strategy to improve therapy because it is superior to radiotherapy alone in other squamous cell carcinomas.

The aim of this study was to retrospectively examine whether the occurrence of squamous cell carcinoma (SCC) antigen tumour marker in the serum has prognostic significance in operable SCC of the cervix at the International Federation of Gynaecology and Obstetrics (FIGO) stages IA2-IIB. A total of 129 patients who had undergone a radical hysterectomy for SCC of the uterine cervix at the Department of Gynecology of the Martin-Luther University, Halle-Wittenberg in 1991-2000 were included. SCC antigen (Ag) was measured by IMx SCC-Ag microparticle enzyme immunoassay (Abbott Laboratories, Abbott Park, IL, USA). To assess the prognostic value of SCC antigen in the serum, we used a step-by-step multivariate analysis based on the Cox proportional hazard regression model. Using a cut-off value of 3.0 ng/ml, we detected preoperative SCC antigen in the serum as an independent prognostic factor in SCC of the cervix, both for recurrence-free and overall survival (P=0.003 and 0.0078). In this retrospective analysis the value of the SCC antigen tumour marker correlates with prognosis in operable SCC of the cervix, independent of tumour size, pelvic nodal status, cervical stroma infiltration, parametrial spread and tumour grading.

In 1999, five randomized studies demonstrated that chemoradiation with cisplatin and low-dose rate (LDR) brachytherapy has a benefit in locally advanced cervical cancer and for surgically treated patients in high-risk situations. We evaluated the safety and efficacy of concomitant chemoradiation with cisplatin and high-dose rate (HDR) brachytherapy in patients with cervical cancer.

Diagnostische Schritte Notwendige und erganzende diagnostische Schritte werden eingeleitet. Die Klinik fur Diagnostische Radiologie bietet neben den kompletten diagnostischen Moglichkeiten auch die bildgestutzte minimal-invasive histologischen Sicherung auf der Basis von Mammographie, Mammasonographie und Magnetresonanztomographie (MRT) mittels Hochgeschwindigkeitsund Vakuumbiopsien an. Benigne Veranderungen konnen im Einzelfall durch die Vakuumbiopsie vollstandig entfernt werden. Bei Indikation zu einer offenen Operation wird bereits jetzt, soweit moglich, das lokoregionare Therapiekonzept diskutiert und festgelegt. Bei Planung eines brusterhaltenden Vorgehens wird bei fast allen Patientinnen mit histologisch gesichertem Mammakarzinom eine praoperative MRTDiagnostik durchgefuhrt. Bei Zusatzbefunden wird zur gezielten Abklarung eine zusatzliche, gegebenenfalls MRT-gestutzte Stanzbiopsie entnommen. Somit erfolgt praoperativ die «Kartierung» der betroffenen Brust und der Ausschluss von kontralateralen Zweitherden. Eine Auswertung des aufwendigen Vorgehens ist derzeit in Arbeit.

Background/Aims: Cytostatics and human antibodies are successfully being used to treat oncological diseases. Despite the beneficial effects of these potent drugs, cardiotoxicity represents one of the most relevant side effects and limits their usage. It is very important to detect cardiotoxicity at an early stage particular in patients under curative chemotherapy to avoid long-term side effects and impairment of quality of life. The aim of this prospective study was to investigate the value of natriuretic peptides and troponin for early detection of cardiotoxicity. Patients and Methods: In this single-center study, 99 cancer patients under treatment with anthracyclines, taxanes, and/or trastuzumab were prospectively included. Clinical examination, echocardiography, and blood sampling (brain natriuretic peptide (BNP), N-terminal-proBNP, and troponin I) were performed at baseline and at 3 and 12 months, respectively. Cardiotoxicity was defined as clinical or echocardiographic signs of heart failure as defined by an increment in New York Heart Association (NYHA) class by more than one and a decline in left ventricular ejection fraction (LVEF) depending on baseline situation. Results: During the 12-month follow-up, 27 patients presented with at least one predefined endpoint. Neither BNP, nor NT-proBNP, nor troponin I was related to the incidence of cardiotoxicity as defined by the combined endpoint. In post-hoc analysis a significant association between an increasing NYHA stage and a decrease in LVEF was found (negative predictive value of 91%). Conclusion: The occurrence of cardiotoxicity could not be detected either by natriuretic peptides or troponin. However, we hypothesize that an increase of more than one NYHA stage as a marker for dyspnea may be an indicator of cardiotoxicity.

5608 Background: Recently, the standard of minimal pathological resection margin distance of 8mm in surgery for primary vulvar cancer has been challenged since several single center analyses failed...

5562 Background: Incomplete surgical staging was shown to be a negative prognostic factor for patients with borderline ovarian tumors (BOT). However, little is known about the prognostic impact of each individual staging procedure. Methods: Clinical parameters of 950 patients with BOT (confirmed by central reference pathology) treated between 1998 and 2008 in 24 German AGO centers were analyzed. Staging quality was evaluated following German guidelines. In patients with adequate surgery regarding their reproductive organs (bilateral salpingo-oophorectomy or intended fertility preserving surgery in patients ≤55 years), other recommended staging procedures (omentectomy, peritoneal biopsies, cytology, and, for mucinous histology, appendectomy) were evaluated applying uni- and multivariate regression models with respect to progression-free survival (PFS), separately for serous and mucinous histology. Results: A total of 559 serous BOT (64.1%) were opposed to 268 mucinous BOT (30.7%). For patients with serous ...

Sertoli-Leydig cell tumors belong to the group of sex-cord stromal tumors of the ovary. They account for less than 0,5% of all ovarian neoplasms. The majority of these tumors are benign, and almost all are localised unilaterally. Herewith, we describe an ovarian Sertoli-Leydig cell tumor in an 11-year-old girl. Serum levels of estradiol and progesterone were mildly elevated. while testosterone and androstendion levels were raised to around three- and sevenfold upper normal limit respectively on presentation. A left salpingo-oophorectomy was performed. Microscopically, the tumor was intermediately differentiated. At 6 months follow-up, there was neither clinical nor sonographical evidence of recurrence, and almost all sex hormone levels had returned to within normal range. Treatment of this pathological entity has to be individualized according to patient age, stage of tumor and degree of differentiation.

5531 Background: Prognosis of node-negative vulvar cancer is generally favorable compared to node positive disease. However, a small proportion of node-negative pts experience early recurrence with subsequent need for radical interventions. Aim of this analysis was to identify possible prognostic factors in this subset of pts. Methods: The AGO CaRE 1 study was designed as retrospective survey of treatment patterns and prognostic factors in vulvar cancer. Pts with primary squamous-cell vulvar cancer stage ≥1b treated at 29 gynecologic cancer centers in Germany 1998-2008 were included in a centralized database. Results: A total of 1618 pts were documented, 802 were node negative (pN0) after surgical staging and further analyzed. Median age was 66 yrs (21-94); 399 (49.8%) had pT1b, 365 (45.5%) pT2, 36 (4.5%) pT3 and 1 pT4 tumors; in 1 pt tumor stage was unknown. Median tumor size was 20 mm (1–345) and depth of invasion 4 mm (0.75–60). 703 (87.7%) pts had an R0 resection with a minimal margin of 5 mm (0.2–33); there were 46 R1 (5.7%) resections and 53 (6.6%) pts with unknown margin status. 692 pts (86.3%) received a full groin dissection (178 after sentinel node dissection) and in 85 pts (10.6%) only a sentinel node procedure was performed; surgery type was unknown in 25 pts (3.1%). 73 pts (9.1%) underwent adjuvant radiotherapy to the vulva. Median follow-up was 40 months. 169 pts (21.1 %) developed disease recurrence (thereof 111 (65.7%) at the vulva only and 53 (31.4%) at other locations, in 5 cases the localization was unknown) after a median of 17.7 months. 101 pts (12.6 %) died. To assess potential prognostic factors, multivariate analyses were performed including age, stage, tumor size, invasion depth, tumor grade, resection margin, adjuvant radiation, and mode of groin dissection [sentinel vs. full]) showing age as the only consistent prognostic factors for recurrence-free and overall survival. Conclusions: Even in the very large patient cohort of the AGO-CaRE database with more than 800 node-negative pts it was not possible to identify reliable clinicopathologic prognostic factors for node-negative disease. Identification of new biological markers will therefore be necessary to select high risk node negative pts for adjuvant treatment.

5007 Background: While the majority of patients with vulvar cancer can be cured by surgery alone, women with lymph-node metastases often show unfavorable outcome. Improved treatment strategies are therefore strongly needed. Methods: Patients with primary squamous-cell vulvar cancer treated at 29 gynecologic cancer centers in Germany between 1998 and 2008 were included in a centralized database and analyzed retrospectively. Results: A total of 1,637 patients were documented with a median follow-up of 121 months. UICC-Stage distribution was 597 (36.5 %) T1, 816 (49.8 %) T2, 160 (9.8 %) T3 and 31 (1.9 %) T4, 33 (2.0 %) were missing. 491 patients had lymph-node metastasis to the groins (N+). 214 N+ patients (43.6 %) developed recurrent disease within a median of 21.4 months. 190 N+ patients (38.7%) died, median overall survival (OS) was 43.4 months, compared to 212 months for node-negative patients. An increasing number of metastatic lymph-nodes was associated with shorter OS: 169 (34.4%) patients had 1, 101 (20.6%) patients 2, 62 (12.6%) patients 3 and 86 (17.5%) patients >3 positive lymph-nodes, with a corresponding OS of 22.4, 17.2, 18.4 and 10.2 months, respectively (for 73 patients the number of nodes was not available). 240 N+ patients were treated with adjuvant radiotherapy (85.8%) or radiochemotherapy (14.2%). Median OS in these patients was significantly longer (66.9 months) compared to N+ patients without adjuvant treatment (35.7 months), the corresponding hazard ratio (HR) was 0.72 (95 % CI: 0.53 - 0.97 p = 0.029). This impact on OS remained consistent in multivariate analysis adjusted for age, ECOG, stage, grading, invasion depth and number of positive nodes (HR 0.68; 95% CI: 0.49 - 0.94 p = 0.020) and was observed irrespective of the number of affected nodes. Conclusions: To this day, this is the largest multicenter study on vulvar cancer. Our findings strongly suggest that the unfavorable prognosis of patients with node positive vulvar cancer can be improved by adjuvant therapy irrespective of the number of affected nodes. As adjuvant radiochemotherapy was shown to be superior to radiotherapy alone in many other squamous cell carcinomas, we are preparing a prospective phase III trial in node-positive vulvar cancer (AGO-CaRE 2 trial).

5031 Background: We present the efficacy data from a phase III study of topotecan (T) plus carboplatin (C) versus standard therapy with paclitaxel plus carboplatin (PC) or gemcitabine plus carboplatin (GC) or carboplatin plus pegylated doxorubicin (PLDC). Methods: From 02/07 to 12/09, 590 pts were screened and 550 pts were randomized to either T (0.75mg/m²/d1-3/q21d) + C (AUC 5/d1/q21d) or to standard therapy with CP or GC or PLDC based on patient preference. Progression free survival at 1 year was defined as primary endpoint. Results: Median number of cycles was 6 (range 0-9) in both arms. Most patients preferred GC (78%) in the standard therapy arm.. Best Response (CR+PR) was 73.1% (95%CI) and 75.1% (95%CI) for the CA. Median follow-up was 18 (0-52) months for TC and 20 (0-48) months for standard therapy. TC failed to show any advantage regarding 1-yr.-PFS or OAS. Conclusions: The combination of topotecan plus carboplatin failed to improve PFS or OAS in platinum sensitive relapsed ovarian cancer. In addition, carboplatin plus gemcitabine was well tolerated with lower rates of severe and long-lasting (neuropathy) toxicities compared to paclitaxel-carboplatin. [Table: see text]

5532 Background: Fulvestrant (F) is a pure anti-estrogen with no agonistic action and no known adverse effects on the endometrium. This may be an advantage over tamoxifen, which has been successfully used in the treatment of hormone-receptor (HR) positive recurrent or metastatic endometrial carcinoma. Methods: This was an open label single-arm multicentre phase II study (AGO-Uterus 5) in patients with recurrent or metastatic endometrial carcinoma and measurable disease (RECIST). Pts. received monthly 250 mg F i.m. injections. The primary objective was clinical response after 3 injections, measured 4 weeks after injection 3 (ITT-pop.). Safety and tolerability were secondary endpoints. Results: Between March 2003 and May 2006, 35 pts. were included. Mean age was 70 years (range 45–83), first diagnosis was a mean 2.6 years ago, diagnosis of recurrence 10.2 months ago. 25 pts. (73.5%) had a FIGO 4B; 24 pts. (71%) had endometrioid cancer, 5 (15%) serous and 5 other carcinoma. All pts. had a positive ER and/or PgR status. 1 pt. had received no surgery for her disease; 21 pts. (61.8%) had prior radiotherapy; 13 pts. (38.2%) chemotherapy. 26 pts. were assessed as planned (ITT); 5 pts. received fewer than 3 injections, 4 pts. were not seen 4 weeks after inj. 3. Response to F was PR in 5 pts. (19.2%) and SD in 8 pts. (30.8%), adding up to a 50% disease control rate. 13 pts. had PD. Tolerability was good, no previously unknown side effects occurred. Conclusions: F showed encouraging response rates in our patient collective and was well tolerated. Further studies are warranted with F in HR pos. endometrial carcinoma. This study was supported by AstraZeneca. F is licensed for treatment of ER+, advanced breast cancer after an antioestrogen in postmenopausal women. [Table: see text]

5121 Background: Patients with advanced cervical cancer frequently suffer from anaemia. Additionally, concomitant anaemia is aggravated by radiochemotherapy (RCT). Study Objectives: This study aime...

Materials and Methods: From 1995 through 1999, a total number of 87 patients with squamous cell cervical cancers (FIGO stages IIB to IVA) underwent definitve radiotherapy (external beam 45-50.4Gy in 1.80Gy-fractions plus HDR-brachytherapy, 5 fractions of 7Gy in point A) in our department. All patients underwent oxygenation measurements with the Eppendorf device prior to treatment and after 19.8Gy external beam XRT. Various histological factors (including the microvessel density) and the S-phase-fraction (flow cytometry) were determined from pretreatment biopsies .