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).
5538 Background: Identification of families at risk for OC including recommendation for prophylactic surgery is the only effective method to reduce OC mortality. In addition, BRCA1/2 mutations are known as prognostic factor and target for treatment. Methods: Prospective counseling and testing of consecutive patients with first diagnosis or platinum sensitive relapse of invasive epithelial OC in Germany. Testing included 25 risk genes related to ovarian cancer (incl. BRCA1, BRCA2, ATM, PALB2, RAD51C, RAD51D, TP53, MLH1, MSH2, MSH6, PMS2). A positive mutation was defined as class 4/5 mutation and a positive family history (FH) was defined as at least one relative with breast cancer (BC) or OC or BC in personal history. Results: In total, 529 pts entered the study, of which 507 were analyzed so far: 270 (53%) patients with first diagnosis of OC and 237 (47%) patients with platinum sensitive relapse. Median age at registration was 61 years (range 18-93). In total, 21% were BRCA1/2 positive (BRCA positive) and 27% for a mutation in at least one risk gene. The incidence of mutations in BRCA1 was 15%, BRCA2: 6%, RAD51C: 1.8%, PALB2: 1.2%. Mutations in all others were found less frequently ( < 1%). Mutations in Lynch syndrome associated genes were found in 0.6%. The incidences did not differ significantly between patients at first diagnosis (BRCA1/2 positive: 19% / risk gene positive: 25%) and relapse (BRCA1/2 positive: 22% / risk gene positive: 30%). Histological subtype and grading were available for 439 patients (87%). The incidence of BRCA / risk gene in high grade serous OC (364/439; 83%) was 23% / 30% and 9% / 19% in all other histological subtypes (75/439; 17%) (p = ns). In elderly patients ( > 70 years at diagnosis), 13% carried a mutation in a risk gene compared to 31% of patients ≤ 70 years (p < 0.001). For 434 pts (86%) FH was evaluable. Of these, 42% had a positive FH. FH identified 69% of the BRCA1/2 positive patients, but missed 31%. Conclusions: 27% of all OC pts harbor a positive mutation in the genes analyzed. Age and FH are insufficient for identifying these patients. Genetic testing should therefore be offered to every patient with invasive epithelial ovarian cancer; limiting testing to BRCA1/2 analysis seems insufficient. Clinical trial information: NCT02222883.
Zusammenfassung Die Twin Reverse Arterial Perfusion (TRAP) Sequenz ist ein komplexes Fehlbildungssyndrom bei monochorialen Mehrlingsschwangerschaft, die durch vaskuläre Anastomosen und partielle oder vollständige Fehlbildung des Herzens und der Extremitäten eines Feten charakterisiert ist. Dies führt zu einer hämodynamischen Abhängigkeit des parasitären Zwillings (Akzeptor) vom „Pump-Zwilling“ (Donor). Ziel des Managements ist, die Überlebenschancen des Pump-Zwillings zu maximieren. Der optimale Zeitpunkt für die Behandlung mittels Radiofrequenz-Ablation oder ultraschallgesteuerter Laserkoagulation ist unklar, internationale wird häufig eine Intervention vor der 16. SSW empfohlen. Wir berichten über die Entbindung bei einer bis dahin nicht diagnostizierten und damit im klinischen Verlauf besonderen monochorial-monoamnioten Geminischwangerschaft in der 34. SSW in unserem Perinatalzentum und zeigen die beeindruckende Maximalausprägung einer untherapierten TRAP-Sequenz.
Background Phase III trial data have shown a significant benefit by the addition of a maintenance treatment with niraparib, irrespective of BRCA or HRD status, in patients with advanced high-grade ovarian cancers; and, a significant benefit of the combination of olaparib and bevacizumab compared with bevacizumab monotherapy in HRD positive patients. However, it is unclear whether a PARP inhibitor monotherapy is sufficient, or if the addition of bevacizumab is needed. Primary Objectives This trial will investigate if the treatment strategy of carboplatin/paclitaxel/bevacizumab/niraparib is superior to the treatment of carboplatin/paclitaxel/niraparib in an all-comer population. Study Hypothesis Adding bevacizumab to chemotherapy followed by niraparib maintenance improves progression-free survival in patients with newly diagnosed advanced ovarian cancer. Trial Design AGO-OVAR 28/ENGOT-ov57 is an international, multicenter, randomized, prospective phase III trial within the the European Network for Gynecological Oncological Trial (ENGOT), led by the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) study group. All patients should have completed the first cycle of chemotherapy (carboplatin and paclitaxel) as part of the Study Run-In-Period. Prior to day 1 of cycle 2, patients with a valid central tumor BRCA (tBRCA) test result were randomized in a 1:1 ratio into either: Arm 1, to receive five additional cycles of carboplatin and paclitaxel q21d, followed by niraparib for up to 3 years; or Arm 2, to receive five additional cycles of carboplatin and paclitaxel plus bevacizumab q21d, followed by bevacizumab q21d (for up to 1 year), and niraparib for up to 3 years. Major Inclusion/Exclusion Criteria The trial population is composed of adult patients with newly diagnosed, advanced high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer FIGO III/IV (except FIGO IIIA2 without nodal involvement). Patients who are scheduled for neoadjuvant chemotherapy and interval debulking surgery are also eligible for the trial. Primary Endpoint The primary endpoint is progression-free survival. Sample Size The study plans to recruit 970 patients (485 patients in each arm). Estimated Dates For Completing Accrual And Presenting Results The Last-Patient-In is expected to be enrolled in September 2024, with presentation of the primary endpoint in 2028. Trial Registration NCT05009082 ; EudraCT Number: 2021-001271-16
The quality assurance program for ovarian cancer (QS-OVAR) evaluates the implementation of treatment standards and impact on survival for International Federation of Gynecology and Obstetrics (FIGO) stage I ovarian cancer.Patients with a first diagnosis of ovarian cancer, diagnosed in the third quarter of 2004, 2008, 2012, and 2016, were documented. Surgical quality was categorized as optimal (maximum one surgical item missing) versus suboptimal (≥2 surgical items missing). Chemotherapy was defined as optimal according to national guidelines. Treatment quality was classified into four categories: surgery and chemotherapy were optimal, optimal surgery and suboptimal chemotherapy, suboptimal surgery and optimal chemotherapy, and surgery and chemotherapy were suboptimal.In total, 19.9% (n=700) of ovarian cancer patients were diagnosed with FIGO stage I. Median age was 60 years (range 18-96), 47.1% had FIGO stage IA and 47.9% had stage IC, with 37.1% high grade serous histology. Optimal surgical quality increased over time from 19.9% to 54.1%. The optimal surgery population increased from 42.2% to 70.9%. Disease free survival improved significantly in the optimal surgery population (84% after 48 months vs 71% in the suboptimal surgery population). Overall survival increased with 91% after 48 months in the optimal surgery population versus 76% in the suboptimal surgery population. In total, 20.7% of patients were undertreated concerning systemic treatment and 1% overtreated. Optimal chemotherapy standard was administered increasingly over time (71.4-80.8%). Disease free survival and overall survival were prolonged with adjuvant chemotherapy. The optimal surgery/chemotherapy subgroup increased from 37.9% to 54.1% with significantly longer disease free survival and overall survival (overall survival at 48 months: optimal surgery and chemotherapy 93%; suboptimal surgery and chemotherapy 68%).Although QS-OVAR data showed that the quality of therapy has improved over the years, not all surgical standards were met in nearly 50% of patients. The steady increase in the optimal surgery and chemotherapy collective is an important tool for improvement of prognosis of ovarian cancer patients.
Bisher existiert keine Level I Evidenz, dass eine systematische pelvine- und paraaortale Lymphadenktomie (LNE) beim fortgeschrittenen Ovarialkarzinom (OvCa) und klinisch negativen Lymphknoten (LK) die Prognose verbessert.
Fragestellung: Diese Subgruppenanalyse der AGO-CaRE-1 Studie untersucht den Einfluss des pathologischen Resektionsrandes auf das Rezidivrisiko beim Vulvakarzinom. Hintergrund ist die Infragestellung des derzeitigen Standards von 8 mm durch kleinere Fallserien.
In the last 5 years there has been much discussion about the surgical procedure for uterine fibroids, and essentially, also uterine sarcoma. Still there exists no reliable presurgical diagnostic tool to differentiate between benign fibroids and uterine sarcomas. The aim of this study was to confirm the suspected association between intraoperative spread of tumor by morcellation and impaired outcomes in patients with sarcoma.After the local ethics commission positively reviewed the study protocol, the oncologic database of our university hospital was retrospectively reviewed for patients with uterine sarcomas over a time period of 13 years (2002-2015). Data was extracted from the medical files and survival information was collected by contacting the patient’s general practitioners if last follow-up-status was older than 6 months. For the analysis, patients were split into two groups with either intrasurgical morcellation (M+) or no morcellation (M-) regarding information provided by the surgical report.Data on 57 patients with uterine sarcoma were available for further analysis. The median age and body mass index of the patients was 63 years and 27 kg/m², respectively. The sarcoma subtypes were 25 leiomyosarcoma, 19 carcinosarcoma, 9 endometrioid stroma sarcoma, 3 adenosarcoma, and one case without further differentiation. In the majority, no morcellation was performed (M- group, n=44) and 51 patients received open surgery (3 laparoscopic, 1 vaginal, and 2 incomplete surgeries). The median time of follow-up was 31 months. The disease-free survival was 50.5 months and the Cox regression analysis showed a hazard ratio of 3.06 [no significant difference between the two subgroups (p=0.079; 95% confidence interval (CI): 0.9-10.6)]. The overall survival was found as 62.2 months and the Cox regression analysis showed a hazard ratio of 3.216 with a statistically significant difference between the two subgroups (p=0.013; 95% CI: 1.3-8.1).Despite the efforts to find a pre-surgical diagnostic tool, the clinical situation remains unsatisfactory. Overall sarcoma prevalence is low during the last 13 years at our university center, but morcellation occurred in a relevant portion of patients (13 of 57). If sarcoma is suspected or diagnosed then en-bloc resection of the uterus can prolong survival. Thus, morcellation of the uterus and not the surgical technique (en-bloc resection) is the prognostic factor and should be avoided in any suspicious case.
Zielsetzung: Aktuell ist kein Triage-System in der Notaufnahme für gynäkologische Patientinnen in Deutschland validiert. Dieses Projekt zielt darauf ab, die Validität des Manchester-Triage-Systems (MTS) zu evaluieren.
Trials in Progressdemonstrated significant improvement in progressive-free survival (PFS) median (months: 41.8 PCO vs. 12.3 PC; HR=0.46; p=0.0027) and OS median not estimable.Methods: This is a phase 2, double-blind, placebo-controlled, multi centered clinical trial.Patients with International Federation of Gynecology and Obstetrics III/IV epithelial ovarian cancer and serum CA125 ≥50 U/mL receiving neoadjuvant chemotherapy will be randomized.In each arm patients will receive oregovomab/placebo at cycles 1 and 3 in combination with chemotherapy prior to interval debulking surgery (IDS), followed by oregovomab/placebo at cycles 4 and 6 in combination with chemotherapy, and oregovomab/placebo monotherapy at cycle 6 plus12 weeks.The objective of this study is to confirm that the presence of primary tumor and its immune suppressive biology does not interfere with chemoimmunotherapy when oregovomab is administered with initiation (cycle 1) of chemotherapy and not delayed to after the debulking procedure.The primary objective of the study is to evaluate the PFS rate at 12 months.Secondary objectives include investigator assessed overall response rate and disease control rate by RECIST v1.1, PFS, overall survival, response to surgery and safety and tolerability.Exploratory objectives will include measurement of the humoral immune response in patients and assessment of immunopathology and inflammatory cell infiltration (TIL's) in the biopsy at baseline and in the interval debulked tumor specimen, and chemotherapy response score after completion of 3 cycles of study treatment and prior to IDS.The study is being planned to enroll 88 patients from 16 centers and 10 sites have been initiated and no enrolment occurred at time of submission.
