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Background: Recently, a Risk of Ovarian Malignancy Algorithm (ROMA) utilising human epididymis secretory protein 4 (HE4) and CA125 successfully classified patients as presenting a high or low risk for epithelial ovarian cancer (EOC). We validated this algorithm in an independent prospective study. Methods: Women with a pelvic mass, who were scheduled to have surgery, were enrolled in a prospective study. Preoperative serum levels of HE4 and CA125 were measured in 389 patients. The performance of each of the markers, as well as that of ROMA, was analysed. Results: When all malignant tumours were included, ROMA (receiver operator characteristic (ROC)-area under curve (AUC)=0.898) and HE4 (ROC-AUC)=0.857) did not perform significantly better than CA125 alone (ROC–AUC=0.877). Using a cutoff for ROMA of 12.5% for pre-menopausal patients, the test had a sensitivity of 67.5% and a specificity of 87.9%. With a cutoff of 14.4% for post-menopausal patients, the test had a sensitivity of 90.8% and a specificity of 66.3%. For EOC vs benign disease, the ROC–AUC of ROMA increased to 0.913 and for invasive EOC vs benign disease to 0.957. Conclusion: This independent validation study demonstrated similar performance indices to those recently published. However, in this study, HE4 and ROMA did not increase the detection of malignant disease compared with CA125 alone. Although the initial reports were promising, measurement of HE4 serum levels does not contribute to the diagnosis of ovarian cancer.

ObjectivesSentinel lymph node (SLN) detection in ovarian cancer is feasible when tracers are injected before the pathological ovary is resected. This study aims to investigate whether the SLN identification is also feasible in patients whose ovarian tumor has already been resected with injection of the tracer into the ovarian ligaments stumps, i.e. in the event that a frozen section confirms malignancy.MethodsPatients who underwent laparotomy with frozen section confirming an ovarian malignancy, and those who underwent a second staging laparotomy after prior resection of a malignant ovarian mass, were included. Blue dye and a radioactive isotope were injected in the stumps of the ligamentum ovarium proprium and the ligamentum infundibulo-pelvicum. After an interval of at least 15-minutes, the sentinel node(s) were identified using either the gamma-probe and/or blue dye.ResultsA total of 11 patients were included in the study, the sentinel node (SLN) procedure was completed in all 11 patients. At least one SLN was identified in 3 patients, resulting in a rather low detection rate of 27,3%.ConclusionsIn this study we showed that SLN procedure after (previous) resection of the tumor seems inferior to detect sentinel nodes when compared to injection of the tracer in the ovarian ligaments before tumor resection.

Introduction/Background*Locally advanced cervical cancer can be treated by concomitant chemoradiation therapy (CCRT) followed by brachytherapy or by neo-adjuvant chemotherapy followed by surgery (NACT-S). Quality of life (QoL) and sexual health (SH) are important to evaluate after treatment considering the young mean age in affected women and relatively long 5-year survival. This study aims to compare differences in QoL and SH among women treated for locally advanced cervical cancer, after CCRT versus NACT-S.MethodologyIn this academic single centre cross-sectional questionnaire study, we included patients > 18 years with a history of locally advanced cervical cancer, who received either CCRT or NACT-S. QoL and SH were assessed using Dutch questionnaires including the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life core module 30 (QLQ-C30), the cervical cancer module 24 (QLQ-CX24), and sexual health questionnaire (SHQ-22). X2-test and T-test were performed to compare the two groups.Result(s)*We sent the questionnaires to 105 women who were treated at our centre in the period between 01-01-2002 and 31-12-2018. A total of 36 patients (34%; n=12 CCRT; n=24 NACT-S) returned the questionnaire and were included for analysis. Six patients in the NACT-S group also underwent adjuvant CCRT. When comparing the CCRT and NACT-S group, 58% vs. 54% did “not at all” feel limited in their daily activities. QoL on average scored 63% vs. 67% (P= 0.29), in the CCRT and NACTS group respectively. Patients were at least “quite a bit” or “very much” satisfied with their sex life in 25% vs. 54% in the CCRT and NACT-S group, respectively (P= 0.048). A total of 33% vs. 46% did “not at all” communicate with medical professionals about sexual issues in the CCRT and NACT-S group, respectively.Conclusion*QoL did not significantly differ when comparing the CCRT to the NACT-S group. Satisfaction with sexual life was higher in the NACT-S group. QoL and SH should receive more attention in patients with cervical cancer after treatment.Abstract 1109 Table 1Clinical variables. CCRT median (range) NACT-S median (range) Total number of patients 12 24 Age 48 (33-82) 47 (24-71) BMI 24.05 (15-32) 25.2 (20-39) Year of diagnosis 2013 (2008-2018) 2016 (2008-2018) Partner? Yes 9 20 No 3 4

Mirvetuximab soravtansine-gynx (MIRV), a first-in-class antibody-drug conjugate targeting folate receptor α (FRα), is approved for the treatment of platinum-resistant ovarian cancer in the United States. We conducted a phase 3, global, confirmatory, open-label, randomized, controlled trial to compare the efficacy and safety of MIRV with the investigator's choice of chemotherapy in the treatment of platinum-resistant, high-grade serous ovarian cancer. Participants who had previously received one to three lines of therapy and had high FRα tumor expression (≥75% of cells with ≥2+ staining intensity) were randomly assigned in a 1:1 ratio to receive MIRV (6 mg per kilogram of adjusted ideal body weight every 3 weeks) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary end point was investigator-assessed progression-free survival; key secondary analytic end points included objective response, overall survival, and participant-reported outcomes. A total of 453 participants underwent randomization; 227 were assigned to the MIRV group and 226 to the chemotherapy group. The median progression-free survival was 5.62 months (95% confidence interval [CI], 4.34 to 5.95) with MIRV and 3.98 months (95% CI, 2.86 to 4.47) with chemotherapy (P<0.001). An objective response occurred in 42.3% of the participants in the MIRV group and in 15.9% of those in the chemotherapy group (odds ratio, 3.81; 95% CI, 2.44 to 5.94; P<0.001). Overall survival was significantly longer with MIRV than with chemotherapy (median, 16.46 months vs. 12.75 months; hazard ratio for death, 0.67; 95% CI, 0.50 to 0.89; P = 0.005). During the treatment period, fewer adverse events of grade 3 or higher occurred with MIRV than with chemotherapy (41.7% vs. 54.1%), as did serious adverse events of any grade (23.9% vs. 32.9%) and events leading to discontinuation (9.2% vs. 15.9%). Among participants with platinum-resistant, FRα-positive ovarian cancer, treatment with MIRV showed a significant benefit over chemotherapy with respect to progression-free and overall survival and objective response. (Funded by ImmunoGen; MIRASOL ClinicalTrials.gov number, NCT04209855.).

Introduction/BackgroundWe aimed to describe management, complications and survival of malignant bowel obstruction (MBO) in epithelial tubo-ovarian cancer patients. Our primary objective was overall survival, measured in days. MBO complications and management were considered secondary endpoints.MethodologyRetrospective monocentric cohort study at the University Hospitals Leuven, Belgium, between January 1st, 2012 until December 31rd, 2016. All primary epithelial tubo-ovarian cancer patients with MBO were identified. The standard conservative approach of MBO in the University Hospitals Leuven is presented in table 1.Abstract EP877 Table 1Standard conservative approach of MBO in the University Hospitals LeuvenNo oral intake of fluid and food Intravenous fluid therapy 2l/24 h Nasogastric tube when necessary Antiemetics e.g. Alizapride (Litican®) Analgesics Octreotide (Sandostatin®) Corticosteroids e.g. Methylprednisolone (Solumedrol®) Abdominal X-ray every two days Results452 patient files were searched from which 48 patients were included in this study with a total of 84 MBO episodes, (median 1 per patient; range 1–5). Median time interval between two MBO episodes was 59 days (range 2–626). Median hospitalization time was 11 days (range 0–74) per episode. Median time interval between cancer diagnosis and first MBO episode was 342 days (range 0–1155). Further characteristics are noted in table 2.Abstract EP877 Table 2Characteristics of MBO in the study population Characteristic Number (n= 48) Time interval between diagnosis and first MBO episode, days; Median (minimum-maximum) 342 (0–1155) Episodes of MBO, n (%); 1; 2; 3; ≥4 27 (56,25); 12 (25); 4 (8,33); 5 (10,42) Episodes of MBO per patient; Median (minimum-maximum) 1 (1–5) Time interval between MBO episodes, days; Median (minimum-maximum) 58,5 (2–626) Hospitalization time per MBO episode, days; Median (minimum-maximum) 11 (0–74) Time to death since the first episode of MBO, days; Median (minimum-maximum) 101 (3–917) Two complications were registeredbowel perforation and bowel ischemia, each in one episode. Conservative treatment was applied in 73 (87%) episodes, including gastrostomy in 3 (4%) episodes. Operative treatment was necessary in 11 (13%) episodes, including exploratory laparoscopy in 2 (2%) episodes and exploratory laparotomy in 9 (11%) episodes. Only one case of postoperative peritonitis was reported. Total parenteral nutrition (TPN) was administered in 15 (31%) patients only. During the study period 35 patients died within a median time interval of 101 days (range 3–917) since the first MBO (figure 1). There was no significant difference in survival between patient groups regarding TPN use, ascites and obstruction at cancer diagnosis.Abstract EP877 Figure 1Kaplan-Meier plot: survival in days from the first episode of malignant (sub)obstruction tConclusionTubo-ovarian cancer patients with MBO have poor prognosis: 73% of our study population died within a relatively short time interval since the first MBO. The majority of patients with MBO were treated conservatively.DisclosureNothing to disclose.

Introduction/Background*Platinum in combination with paclitaxel (P) and bevacizumab is the standard of care in first-line recurrent/advanced cervical cancer (Tewari, NEJM 2020). Nintedanib is an oral tyrosine kinase inhibitor targeting, among others, vascular endothelial growth factor receptor.MethodologyDouble-blind phase II randomised study in patients with first-line recurrent or primary advanced (FIGO stage IVB) cervical cancer. Patients received carboplatin AUC 5-6 and paclitaxel 175mg/m2 q 3 weeks with oral nintedanib 200 mg BID/placebo. Stratification factor was primary advanced versus recurrent disease. The primary endpoint was progression-free survival (PFS) at 1,5 years with at least 87 events and α=0.15, β=80%, one sided, in favor of the nintedanib (N) versus control (C) arm. The study (NCT02009579) was performed according to the ENGOT model A.Result(s)*120 patients (62 N, 58 C) were randomised between March 2014 and October 2018. Median follow-up was 35 months. Baseline characteristics were similar in both groups (total population: squamous cell carcinoma 62%, prior radiotherapy 64%, primary advanced 25%, recurrent 75%). The primary endpoint was met with a PFS at 1.5 years of 15.1% versus 12.8% in favour of the nintedanib arm (p = 0.057). Median overall survival (OS) was 21.7 and 16.4 months for N and C, respectively. Subgroup analysis did not demonstrate a difference in PFS in the primary advanced setting, but in the recurrent setting the 1 year PFS was 22.8% and 14.9% for N and C, respectively. Confirmed RECIST response rate was 48% for N and 39% for C. No new adverse events were noted for N. However N was associated with numerically more serious adverse events for anemia and febrile neutropenia. Discontinuation of chemotherapy was similar in both groups. N was discontinued in 3% versus placebo in 1.6% of the patients. Dose reduction of N was necessary in 53% of the patients.Conclusion*The study met its primary endpoint with a prolonged PFS in the N arm. No new safety signals were observed.

Introduction/Background*SENTIX is a prospective cohort multicentric international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. SLN frozen section (FS) and pathological ultrastaging were mandatory by the protocol. Samples from SLN were reviewed centrally for pathological assessment quality control. Only sites experienced in SLN biopsy technique could join the trial.MethodologyIn total, 47 sites from 18 countries participated in the trial. Patients with FIGO 2009 stages T1A1/LVSI+ – T1B1 (<4 cm or ≤ 2 cm for fertility sparing), with common tumour types and no suspicious lymph nodes on imaging were registered in the trial. Patients remained in the trial after the surgery if SLN were detected on both sides of the pelvis and if SLN were negative on FS histological evaluation. Blue dye, radioactive tracer, indocyanine green or their combinations were all eligible tracers for SLN detection. Intraoperative SLN pathological processing consisted of SLN examination in one randomly selected slice. SLN ultrastaging protocol included a complete processing of all SLN tissue in slices of 2 mm thickness, 2 sections in 150 μm from each block until no tissue left, one stained with H&E and second examined immunohistochemically.Result(s)*Altogether 733 patients were registered until Sentix enrolment closure in October 2020, 83 patients were excluded (table 1) and 650 patients was analysed. Patients` characteristics are shown in table 1. Bilateral SLN detection rate reached 95%. FS detected macrometastases (MAC) in 44 cases and micrometastasis (MIC) in 4 cases. SLN ultrastaging found additional 9 cases with MAC, 26 with micrometastases (MIC) and all 19 cases with isolated tumor cells (ITC). Sensitivity of FS was 83.0% for the detection of MAC, 57.8% for pN1 status (MAC or MIC) and 47.1% for any type of SLN involvement (MAC, MIC, ITC). Table 2.Abstract 950 Table 1Patient’s characteristics (N=733)Abstract 950 Table 2SLN status assessed by frozen section and final ultastaging (N=650)Conclusion*High bilateral detection rate of 95% was achieved in Sentix sites experienced in the SLN biopsy technique. Intraoperative pathological assessment of SLN failed to detect majority of MIC (86.7%), all cases with ITC and 42.2% with pN1 (MIC or MAC).

ObjectivesPembrolizumab, an anti–PD-1 antibody, has demonstrated activity as monotherapy and in combination with lenvatinib in patients with previously treated mismatch repair (MMR) deficient and MMR proficient endometrial cancer (EC). ENGOT-en11/GOG-3053/KEYNOTE-B21 (NCT04634877) is a phase 3, randomized, double-blind study of pembrolizumab or placebo in combination with adjuvant chemotherapy with/without radiotherapy in patients with EC.MethodsEligible patients are ≥18 years with newly diagnosed high-risk (stage I/II non-endometrioid or with p53 abnormality and any histology, stage III/IVa), previously untreated EC following surgery with curative intent with no evidence of disease post-operatively. ∼990 patients will be randomized to receive pembrolizumab 200 mg or placebo Q3W for 6 cycles plus chemotherapy (carboplatin area under the curve [AUC] 5/6 plus paclitaxel 175 mg/m2 Q3W or carboplatin AUC 2/2.7 plus paclitaxel 60 mg/m2 QW) in stage 1. Patients receive pembrolizumab 400 mg or placebo Q6W for 6 cycles in stage 2. Radiotherapy (external beam radiotherapy [EBRT] and/or brachytherapy) ± radiosensitizing cisplatin 50 mg/m2 (days 1 and 29) may be administered after completion of chemotherapy. Randomization is stratified by MMR status (pMMR vs dMMR) and, within pMMR, by planned radiation therapy (cisplatin-EBRT vs EBRT vs no EBRT), histology (endometrioid vs non-endometrioid), and FIGO surgical stage (I/II vs III/IVA). Dual primary endpoints are disease-free survival (DFS; per investigator assessment) and OS. Secondary endpoints include DFS (per BICR), DFS (per investigator assessment) and OS by biomarker status (PD-L1 and tumor mutational burden), safety, and QoL. Enrollment began December 2020 and is ongoing in 28 countries.ResultsNot applicableConclusionsNot applicable

Introduction/BackgroundSurgical treatment is mutilating and resection often results in involved margins. As a consequence, local recurrences are frequent after surgery.MethodologyRetrospective study of patients with vulvar Paget's disease treated in our hospital between 1993 and 2018.ResultsThirty-one consecutive patients with vulvar Paget's disease were included, whereof twenty patients were irradiated in the primary or recurrent setting. Radiotherapy on the vulva and perineum was performed at a median dose of 60 Gy in fractions of 2 Gy. The median follow-up after radiotherapy was 75 months. Eight (26%) patients underwent as primary treatment radiotherapy only.Only one (13%) had a recurrence (after four months) and was operated. Fifteen (48%) patients had surgery as only primary treatment; five (33%) of them had a recurrence. Four of these had, after 3 or 4 surgical interventions, radiotherapy for recurrence. Only one of these 4, had a relapse after 85 months. Eight (26%) patients had as primary treatment surgery followed by adjuvant radiotherapy (due to positive margins), one (13%) of these recurred and died of disease.ConclusionSurgery is the most commonly used therapy for vulvar Paget's disease, even though it is difficult to excise the disease adequately and often multiple surgeries are necessary. According to our experience, radiotherapy is a good adjuvant treatment option in patients with vulvar Paget's disease with positive resection margins. Moreover, in our experience, primary radiotherapy seemed to be a safe alternative to surgery, that can prevent patients with Paget's disease of the vulva to undergo mutilating and often repeated surgery.DisclosureNothing to discloseAbstract EP1193 Table 1Treatment and recurrences Treatment N Recurrence after primary treatment N (%) Surgical treatment for relapse N (number of re-interventions per patient ) Surgery only 15 5 (33) 4 (2-3-2-3) Radiotherapy only 8 1 (13) 1 (1) Surgery + radiotherapy 8 1 (13) 0

Introduction/BackgroundRecent research has distinguished various molecular classifications for endometrial carcinoma (EC). The Proactive Molecular Risk Classifier for Endometrial Cancer (ProMise, Talhouk, BJC 2015,113:299) classification consists of immunohistochemistry (IHC) (p53 and mismatch repair proteins) and PCR sequencing for Polymerase Epsylon-Extracellular-Domain-Mutations (POLE-EDM).MethodologyNinety-three consecutive endometrial cancer patients, diagnosed between March 2017 and November 2018, were subjected to molecular and immunohistochemical analyses, according to ProMise. IHC for p53 and the mismatch repair proteins (MLH1, PMS2, MSH6 and PMS2) was performed. All patients were also tested for POLE-EDM using PCR, followed by Sanger sequencing (exon 9, 11, 13 and 14).In addition to the ProMise testing, all tumors and corresponding normal tissue of patients with mismatch repair deficient staining on IHC, were tested with PCR using the Microsatellite Instability (MSI) kit (MSI analysis system, Promega). Hypermethylation of MLH1 promotor and the presence of the BRAF p.V600E missense mutation was tested with (methylation specific) multiplex ligation dependent probe amplification.ResultsFIGO classification was stage IA(n=45), IB(n=17)) II(n=8), III(n=17) and IV(n=6). Classification according to histological type is presented in table 1. Of the 28 patients with MMR-D (Mismatch Repair-Deficiency) on IHC, 22(79%) showed hypermethylation as the probable cause of MMR-D. The remaining 6 patients were referred for germline analysis of Lynch syndrome. Five patients carried a pathogenic germline mutation in one of the mismatch repair genes: MSH6(n=3), PMS2(n=1), MLH1(n=1). In one patient no germline mutation was identified, hypothesizing a somatic cause. POLE-EDM was identified in 6 (6%) patients. Double positive status (POLE-EDM+MMR-D or POLE-EDM+p53 abnormal) was observed in 4 patients (4%) (table1).ConclusionThe ProMise classification proved to be an efficient and easily implementable system. In the group with MMR-D, hypermethylation was the cause in 79%. POLE-EDM was identified in 6% of the patients, but its role needs to be clarified in non-endometrioid tumors.DisclosureNothing to disclose.Abstract P88 Table 1Distribution of molecular subgroups among histopathological types. G: grade; MMMT: Malignant Mixed Müllerian TumorHistological type MMR-D on IHC POLE-EDM p53 abnormal p53 wild type MMR-D + POLE-EDM POLE-EDM + p53 abnormal G1-2 Endometrioid EC (n=64) 21 2 3 38 0 0 G3 Endometrioid EC (n=5) 3 0 0 1 1 0 Serous EC (n=11) 1 0 10 0 0 0 Clear cell EC (n=3) 0 0 1 1 1 0 Mixed G3 Endometrioid and serous EC (n=4) 0 0 2 0 1 1 MMMT EC (n=6) 0 0 6 0 0 0 Total (n=93) 25 (27%) 2 (2%) 22 (24%) 40 (43%) 3 (3%) 1 (1%)