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Introduction/Background*High cancer risks, as applicable to BRCA1 and BRCA2 pathogenic variant (PV) carriers, can induce significant cancer concerns. We examined the degree of cancer worry and the course of this worry among BRCA1/2-PV carriers opting for surgery to prevent ovarian cancer, and identified factors associated with high cancer worry.MethodologyCancer worry was evaluated as part of the multicentre, prospective TUBA-study (NCT02321228) in which BRCA1/2-PV carriers choose between the standard risk-reducing salpingo-oophorectomy or a novel strategy, risk-reducing salpingectomy with delayed oophorectomy. The Cancer Worry Scale was obtained before and three and twelve months after surgery. Cancer worry patterns were analysed using latent class growth analysis and factors associated with cancer worry were identified with regression analysis.Result(s)*Of all 577 BRCA1/2-PV carriers, 320 (55.5%) had high (≥14) cancer worry pre-surgery and 70.2% had higher cancer worry pre-surgery than post-surgery. Based on the course of cancer worry, BRCA1/2-PV carriers could be classified into three groups: persistently low cancer worry (56.4%), persistently high cancer worry (6.3%), and fluctuating cancer worry that mainly declined over time (37.3%). Factors associated with persistently high cancer concerns were: age below 35 (BRCA1) or 40 (BRCA2) years, unemployment, previous breast cancer diagnosis, lower education and more recent diagnosis with the BRCA-PV.Conclusion*High cancer worry is common among BRCA1/2-PV carriers and mainly declines after risk-reducing surgery. However, cancer worry remains high in 6% of the women and they should be identified and offered support. It should be realized that in this group, surgery does not reduce cancer concerns.

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).

Introduction/Background*Up to 26% of early-stage cervical cancer patients relapse after primary surgical treatment. However, little is known about the factors affecting prognosis following disease recurrence. Hence, the aim of this study was to evaluate post-recurrence disease-specific survival (PR-DSS) and to identify respective prognostic factors.MethodologyData from 528 early-stage cervical cancer patients who relapsed after primary surgical treatment performed between 2007 and 2016 were obtained from the SCCAN study (Surveillance in Cervical CANcer). Parameters related both to primary disease and recurrence diagnosis were combined to develop a multivariable Cox proportional hazards model predicting PR-DSS.Result(s)*Five-year PR-DSS reached 39.1% (95% confidence interval: 22.7% – 44.5%) with median disease-free survival between primary surgery and recurrence diagnosis (DFI1) of 1.5 years and median survival after recurrence of 2.5 years. Six variables significant in multivariable analysis were included in the PR-DSS prognostic model; two related to the primary disease characteristics: maximal diameter of the tumour and lymphovascular space invasion; and four related to the recurrence diagnosis: DFI1, age, presence of symptoms, and recurrence localization (table 1). C-statistics of the final model after 10-fold internal validation equalled 0.701 (95% CI: 0.675 – 0.727). Five risk groups significantly differing in prognosis were identified, with 5-year DSS after recurrence of 85.6%, 62.0%, 46.7, 19.7%, and 0% in the highest risk group (figure 1).Abstract 942 Table 1Multivariable Cox regression model for prediction of disease-specific death after recurrence Predictor B SE(β) HR 95% CI P-value Points (max. 100) Years from surgery to recurrence > 1 year Reference 0 < 1 year 0.516 0.132 1.676 1.294–2.169 < 0.001 11 Age at recurrence < 65 years Reference 0 65+ years 0.543 0.187 1.720 1.192–2.482 0.004 12 Maximal pathologic tumour diameter* < 0.5 cm Reference 0 0.5–1.9 cm 0.947 0.602 2.577 0.792–8.380 0.116 20 2.0–3.9 cm 1.269 0.593 3.557 1.113–11.374 0.032 27 ≥ 4.0 cm 1.481 0.598 4.397 1.363–14.184 0.013 31 LVSI* No/unknown Reference 0 Yes 0.672 0.148 1.957 1.463–2.619 < 0.001 14 Recurrence symptoms No Reference 0 Yes/unknown 0.788 0.151 2.199 1.634–2.958 < 0.001 17 Recurrence localization Isolated Reference 0 Multiple 0.687 0.135 1.987 1.526–2.587 < 0.001 15 *Characteristics at the time of primary surgeryAbstract 942 Figure 1Disease specific survival of all patients stratified by risk score (N=528). Time zero was set at date of recurrence diagnosisConclusion*We have developed the first robust model of disease-specific survival after recurrence stratifying relapsing cervical cancer patients according to their risk profile using six traditional prognostic markers. The strongest factor related to the length of post-recurrence survival was the largest size of the primary tumour, followed by the presence of symptoms at the time of diagnosis, which remained significant even after correction for lead-time bias.

Introduction/Background*The SENTIX is a prospective cohort international study on sentinel lymph node (SLN) biopsy without pelvic lymph node dissection (PLND) in patients with early-stage cervical cancer. The primary end point is a recurrence rate at 24 months´ follow-up after the surgery. Either magnetic resonance imaging (MRI) or expert ultrasound (EUS) was mandatory as a preoperative staging method. The aim of this study is to report the accuracy of preoperative local staging.MethodologyForty-seven sites from 18 countries participated in the study. Patients with stages T1a1/LVSI+ – T1b1 (FIGO 2009), common histological types and no suspicious lymph nodes on imaging were eligible. Patients were excluded from further study if SLN were not detected on both sides and if SLN was positive on frozen section histological evaluation. Compared were results from preoperative imaging with final pathology reports.Result(s)*From May 2016 to October 2020, 733 registered patients underwent surgery, 132 were excluded intraoperatively, data from 708 were analysed in this study. Patients’ characteristics are in table 1. Out of 90 patients clinically staged as 1A tumours, 42 (46.7%) were upstaged to IB1 (86% ≤ 2 cm, 14% 2-4cm, 0% > 4cm); 76.3% had conisation as diagnostic procedure. Fourteen out of 547 preoperatively IB1 tumours (2.6%) were upstaged to IB2 > 4cm. Analogously 33 patients (6%) with IB tumours were downstaged to IA. Preoperatively unrecognized parametrial involvement was found by pathology only in 22 out of 637 patients (3.5%). EUS and MRI were used equally in the study (53.5% vs 56.1%), both were comparable in the accuracy of tumour size measurement (2 cm size categories shift in stage IB) (p=1.000) and in the failure to detect parametrial involvement (2.9% vs 4.0%) (p=0.535). Chart 1.Abstract 966 Figure 1Chart 1 the accuracy of local stagingAbstract 966 Table 1Patient’s characteristicsConclusion*Clinical staging with EUS and MRI failed to detect positive parametria only in 3.5% of patients in the Sentix trial. Upstaging from IA tumours was frequent, mostly after previous conization. Only 2.6% of patients were upstaged to IB2 tumours >4 cm (IB3 FIGO 2018). Both EUS and MRI were equally reliable in tumour size and parametrial involvement assessment.

Introduction/Background*Current guidelines for surveillance strategy in cervical cancer are rigid, recommending the same strategy for all survivors. The aim of this study was to develop a robust and comprehensive model allowing for individualised surveillance strategy based on risk profile of early-stage cervical cancer patients that were referred for surgical treatment with curative intent.MethodologyThe data of 4,343 cervical cancer patients with pathologically confirmed early-stage cervical cancer treated between 2007 and 2016 were obtained from SCANN consortium centres of excellence (Surveillance in Cervical CANcer). Only patients with complete key predictor variables and a minimum of one-year follow-up data availability were included. Based on the prognostic markers, a multivariable Cox proportional hazards model predicting disease-free survival (DFS) was developed and internally validated. A risk score, derived from regression coefficients of the model, stratified the cohort into significantly distinctive risk groups. On its basis, the annual recurrence risk model (ARRM) was calculated by conditional survival analysis.Result(s)*Five variables significant in multivariable analysis of recurrence risk were included in the prognostic model: maximal pathologic tumour diameter, tumour histotype, tumour grade, the number of positive pelvic lymph nodes, and lymphovascular space invasion (table 1). The model was ten-fold internally cross-validated with the average AUC of 0.732. Five risk groups significantly differing in prognosis were identified: with five-year DFS of 97.5%, 94.7%, 85.2%, and 63.3% in consecutive increasing risk groups, while two-year DFS in the highest risk group equalled 15.4%. Based on ARRM, the annual recurrence risk in the lowest risk group was below 1% in the first year of follow-up and declined below 1% at years three, four, and >5 in the three medium-risk groups (figure 1). The proportion of pelvic recurrences declined in groups with the growing risk. In the whole cohort, 26% of recurrences appeared at the first year of the follow-up, 48% by year two, and 78% by year five.Abstract 960 Table 1Multivariate model for risk of recurrence predictionAbstract 960 Figure 1ARRM: Landmark analysis of the annual probability of recurrence after surgery. N/A not analysed.Conclusion*ARRM represents a powerful tool for tailoring the surveillance strategy in early-stage cervical cancer patients based on the patient´s risk status and respective annual recurrence risk. It can easily be utilised in routine clinical settings internationally.

Introduction/BackgroundRecently published data have renewed the debate on surgical approach (open vs. laparoscopic) in radical hysterectomy and its effect on survival and recurrence. In addition, an estimation of risk factors of surgical complications would be beneficial in the management of these patients. Therefore, we aimed to evaluate possible predictors of short-term surgical complications after radical hysterectomy for early-stage cervical cancer.MethodologyPatients diagnosed with cervical cancer FIGO (2009) stage IB1 and IIA1 between January 2015 and December 2017 who underwent radical hysterectomy with pelvic lymphadenectomy in one of the nine specialized centres in the Netherlands, were identified from the Netherlands Cancer Registry. Patients were excluded if primary treatment consisted of simple hysterectomy (i.e. without parametrial dissection) or radical trachelectomy. Complications and type of complications, developing within 30 days after surgery, were registered. Multivariable logistic regression analysis was used to identify predictors for surgical complications.ResultsOf the 472 patients, 166 (35%) developed surgical complications. Predominant FIGO stage was IB1 (97%), mean age was 45±12 years, mean body mass index was 26±5 kg/m2. Most patients were treated with open surgery (58%). The most frequent complications were urinary retention with catheterisation in 73 patients (15%) and excessive perioperative blood loss >1000 mL (EBL) in 50 patients (11%) (table 1). Open surgery, chronic pulmonary disease, vascular disease and medical centre emerged as independent predictors of the occurrence of complications (table 2). BMI was found as negative predictor for urinary retention. Open surgery and BMI were found to be independent predictors for EBL.ConclusionWe conclude that open surgery, chronic pulmonary disease, vascular disease and BMI negatively affect the occurrence of short-term surgical complications. We believe these findings should also be taken into consideration, together with data on survival and recurrence, in the choice of surgical approach.DisclosureNone of the authors received financial support for the research and/or authorship of this article. Hans Wenzel - Nothing to disclose; Toon van Gorp - Nothing to disclose; Ruud Bekkers - Nothing to disclose; Cor de Kroon - Nothing to disclose; Luc van Lonkhuijzen - Nothing to disclose; Leon Massuger - Nothing to disclose; Hans Nijman - Grant Dutch Cancer Society; Stock owner SME Vicinivax; Grant Aduro; Ramon Smolders - Nothing to disclose; Nienke van Trommel - Nothing to disclose; Refika Yigit - Nothing to disclose; Ronald Zweemer - Proctor Intuitive Surgical; Roy Kruitwagen - Nothing to disclose; Maaike van der Aa - Nothing to disclose;Abstract P46 Table 1Short-term surgical complications, organised by categoryAbstract P46 Table 2Multivariable logistic regression analysis of risk factors for the occurrence of short-term surgical

Introduction/BackgroundAdult granulosa cell tumours (aGCT) constitute a rare subtype of ovarian cancer, with >90% of tumours characterized by the FOXL2 c.402C>G mutation. Recurrences occur in nearly 50% of patients and are associated with a poor prognosis. Surgery is the mainstay of treatment, since the effect of adjuvant therapies are limited. Chemotherapy and hormone therapy response is difficult to predict and patient numbers insufficient to conduct informative clinical trials. Patient-specific aGCT organoid and 2D culture establishment could evaluate the effect of novel therapeutic options on a relatively large scale and enable personalized treatment in this neglected patient group.MethodologySamples from 46 tumours (4 primary and 42 recurrences) from 18 patients were collected, mechanically homogenized to single cells and small tissue pieces, and seeded in 50% Cultrex Basement Membrane Extract on day of surgery. Basal medium (DMEM/F12) supplemented with various growth factor combinations promoted organoid formation. Medium was refreshed every 3–4 days and cells passaged every 3 weeks. In parallel, 2D monolayer cell cultures were established to perform drug screens for later validation in the more physiologically relevant organoids as they became available. Organoid and 2D tumour origin verification is ongoing by FOXL2 c.402C>G PCR.ResultsTumour tissue cultivation resulted in 3D structures that remained viable for 3–4 passages, with an establishment rate of approximately 75% in primary and 26% in recurrences. Morphology of masses ranged from grape-like to cystic, with primary organoids demonstrating a more cystic morphology (figure 1) that could be robustly passaged. Monolayer cultures in DMEM/F12/FBS were successfully established for future drug screening with carboplatin, paclitaxel, tamoxifen and other first-line treatments.ConclusionPatient-derived aGCT organoids can be established. Organoid establishment is more successful for primary tumours than for metastases, and organoid establishment optimization is necessary. Tumour cell culture establishment and drug screens are likely to provide insight into patient-specific treatment response.DisclosureNothing to disclose.Abstract P174 Figure 1Organoids (black arrows) derived from primary tumor tissue. Passage III

Background Surgical site infections (SSI) are frequent complications after elective abdominal surgery. We designed the Enhanced PeriOperative Care and Health Protection programme (EPO 2 CH) care bundle, comprising of intraoperative high fractional inspired oxygen; intraoperative goal-directed fluid therapy; active preoperative, intraoperative and postoperative warming; glucose control and treatment of hyperglycaemia (> 10 mmol L − 1 ) in diabetics as well as non-diabetics; and wound irrigation before closure using an aqueous antiseptic. We hypothesise that EPO 2 CH added to standard care reduces the incidence of SSI compared to standard care alone for elective abdominal surgery. Methods This trial is designed as an open label, pragmatic randomised controlled parallel-group multicentre superiority trial. The primary endpoint is the incidence of SSI, defined by the Centers for Disease Control and prevention, within 30 days after surgery. The incidence of SSI is assessed using the Dutch national complication register and medical chart review. Secondary endpoints include the SSI incidence within 90 days, incidence of anastomotic leakage at 30 and 90 days, the incidence of incisional hernia within 1 year, mortality within 1 year and 5 years, quality of life, health and disability, and cost-effectiveness. Primarily, an intention-to-treat analysis will be performed to estimate the relative risk using a log binomial model. If not feasible, a logistic regression will be used to estimate the odds ratio. A per-protocol analysis will also be performed. Furthermore, the attributive effect of the distinct interventions will be explored. Discussion The results of the EPO 2 CH trial will determine if the EPO 2 CH bundle is effective to prevent SSI incidence for patients undergoing elective abdominal surgery. Details of the statistical analysis are described in this Statistical Analysis Plan (SAP). Trial registration Registration number: Dutch Trial Register Trial NL5572 . Registered on March 3, 2016. SAP version: V1.0, January 8, 2020. This SAP has been written based on study protocol V10.

Introduction/BackgroundSENTIX is a prospective cohort multicenter 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. Samples from SLN were reviewed centrally for pathological assessment quality control. Only sites experienced in SLN biopsy technique were eligible.MethodologyIn total, 47 sites from 18 countries participated in the study. Patients with stages T1a1/LVSI+ - T1b2 (<4 cm or ≤2 cm for fertility sparing), with common tumor types and no suspicious lymph nodes on imaging were pre-registered in the study. Patients remained registered after the surgery if SLN were detected on both sides and if SLN were negative on frozen section. Blue dye, radioactive tracer, indocyanine -green (ICG) or their combinations were all eligible tracers for SLN detection. 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.ResultsData from 372 patients were analyzed who were pre-registered at the time when the number of cases treated per protocol reached 300. Patient characteristics are shown in table 1. Bilateral detection rate reached 91%. table 2 shows factors influencing SLN detection. Frozen section detected macrometastases (MAC) in 22 cases. SLN ultrastaging found additional 7 cases with MAC, 19 with micrometastases (MIC) and 11 with isolated tumor cells (ITC). Sensitivity of FS was 75.9% for the detection of MAC and 37.3% for any type of SLN involvement.ConclusionHigh bilateral detection can be achieved in sites experienced in the SLN biopsy technique. We did not confirm a higher detection rate using ICG. FS failed to detect 26/48 (54%) of cases with MIC or MAC in SLN.DisclosureThis work was supported by a grant from the Czech Research Council (No 16-31643A). Conflict of interest: None of the authors declare a conflict of interest.Abstract EP334 Table 1Preoperative characteristics of patients (N=372)Abstract EP334 Table 2Factors influencing bilateral detection rate of SLN

Introduction/Background*The impact of lymph node (LN) micrometastases (MIC) in cervical cancer patients remains a controversial topic given their low incidence and good prognosis of patients managed by primary surgery.We aim to evaluate the prognostic significance of MIC and isolated tumour cells (ITC) in a large cohort of patients from the SCCAN retrospetive study (Surveillance in Cervical CANcer). SCCAN study analysed data from more than 4300 patients with early stage cervical cancer treated by primary surgery at 20 large tertiary institutions from Europe, North America, South America and Australia.MethodologyIn this SCCAN sub-study, we included patients with early stage cervical cancer (T1a1 LVSI+ – T2b) treated between 2007 and 2016 with at least 1-year follow-up data availability, who underwent primary surgery including sentinel lymph node (SLN) biopsy and in whom SLNs were processed by pathological ultrastaging protocol.Result(s)*Out of 969 included patients with at least 1 SLN detected, 174 (18%) had positive LN (table 1). Maximal tumour diameter >2cm, positive LVSI, grade ≥ 2, uncommon histological type (neuroendocrine, sarcoma, etc.) and macrometstasis (MAC) or MIC in LN were factors associated with significantly decreased five-years disease free survival (DFS) (table 2). MAC, MIC or ITC was the largest LN metastasis in 84 (9%), 59 (6%) and 31 (3%) cases respectively. Adjuvant (chemo)radiation was administred in 89%, 85% and 58% of patients with MAC, MIC and ITC. DFS reached 75%, 73% and 83% in patients with MAC, MIC and ITC compared with 90% in the N0 patients. Patients with MAC and MIC had significantly decreased DFS than those with N0 disease (HR=2.36 and 2.55).Abstract 898 Figure 1Abstract 898 Table 1Data summary (N = 969) Characteristics Description Tracer type Radiocolloid 423 (43.7%) Dye 662 (68.3%) ICG 220 (22.7%) No. of SLN detected Mean ± SD 3.2 ± 2.2 Largest type of metastasis in LN including SLN Negative 795 (82.0%) ITC 31 (3.2%) MIC 59 (6.1%) MAC 84 (8.7%) Surgical approach Open 575 (59.3%) Robotic 195 (20.1%) Laparoscopic 199 (21.5%) Tumour histotype Squamous 605 (62.4%) Adenocarcinoma 287 (29.6%) Adenosquamous 50 (5.2%) Neuroendocrine 18 (1.9%) Other 9 (0.9%) Grade 1 149 (15.4%) 2 406 (41.9%) 3 246 (25.4%) N/A 168 (17.3%) LVSI No 316 (32.6%) Yes 351 (36.2%) N/A 302 (31.2%) Maximal pathologic tumour diameter [mm] Mean ± SD 20.6 ± 13.7 Median (IQR) 19 (10; 30) < 0.5 cm 73 (7.5%) 0.5–1.99 cm 424 (43.8%) 2–3.99 cm 376 (38.8%) ≥ 4 cm 96 (9.9%) Adjuvant therapy 312 (32.2%) if yes: radiotherapy 153 (49.0%) chemoradiotherapy 136 (43.6%) chemotherapy 18 (5.8%) chemoradiotherapy + chemotherapy 5 (1.6%) Recurrence 117 (12.1%) Abstract 898 Table 2Univariate analysis of factors associated with disease-free survival (N = 969) Predictor Category n HR (95% CI ) p-value Surgical approach Open 575 Ref. Robotic 195 1.21 (0.74; 1.97) 0.439 Laparoscopic 141 1.51 (0.93; 2.45) 0.097 Combined 58 1.06 (0.48; 2.31) 0.888 Tumour diameter < 0.5 cm 73 Ref. 0.5–1.99 cm 424 1.67 (0.51; 5.47) 0.399 2–3.99 cm 376 3.98 (1.25 ; 12.69) 0.019 ≥ 4 cm 96 6.35 (1.91 ; 21.13) 0.003 LVSI No 316 Ref. Yes 351 2.31 (1.47 ; 3.63) < 0.001 Tumour histotype Squamous 605 Ref. Adenocarc. 287 1.13 (0.75; 1.71) 0.554 Adenosquamous 50 1.38 (0.66; 2.89) 0.385 Other 27 3.03 (1.45 ; 6.31) 0.003 Grade 1 149 Ref. 2 406 2.08 (1.02 ; 4.22) 0.044 3 246 3.35 (1.64 ; 6.85) < 0.001 Largest type of metastasis in LN Negative 795 Ref. ITC 31 1.67 (0.68; 4.14) 0.264 MIC 59 2.55 (1.47 ; 4.43) < 0.001 MAC 84 2.36 (1.44 ; 3.87) < 0.001 Largest type of metastasis in LN Negative 795 Ref. ITC 31 1.67 (0.68; 4.14) 0.264 MIC+MAC 143 2.44 (1.63 ; 3.64) < 0.001 Conclusion*Early-stage cervical cancer patients with MIC in pelvic LN have significantly decreased DFS. Their management should follow the same principles as in patients with MAC.