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At the time of AtTEnd trial design, standard treatment for advanced or recurrent endometrial cancer included carboplatin and paclitaxel chemotherapy. This trial assessed whether combining atezolizumab with chemotherapy might improve outcomes in this population. AtTEnd was a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial done in 89 hospitals in 11 countries across Europe, Australia, New Zealand, and Asia. Enrolled patients were aged 18 years or older, and had advanced or recurrent endometrial carcinoma or carcinosarcoma, an Eastern Cooperative Oncology Group performance status of 0–2, and received no previous systemic chemotherapy for recurrence. Patients were randomly assigned (2:1) using an interactive web response system (block size of six) to either atezolizumab 1200 mg or placebo given intravenously with chemotherapy (carboplatin at area under the curve of 5 or 6 and paclitaxel 175 mg/m2 intravenously on day 1 every 21 days) for 6–8 cycles, then continued until progression. Stratification factors were country, histological subtype, advanced or recurrent status, and mismatch repair (MMR) status. Participants and treating clinicians were masked to group allocation. The hierarchically tested co-primary endpoints were progression-free survival (in patients with MMR-deficient [dMMR] tumours, and in the overall population) and overall survival (in the overall population). Primary analyses were done in the intention-to-treat population, defined as all randomly assigned patients who gave their full consent to participation in the study and data processing. Safety was assessed in all patients included in the intention-to-treat population who received at least one dose of study treatment. Here, we report the primary progression-free survival and the interim overall survival results. This study is ongoing and is registered with ClinicalTrials.gov, NCT03603184. Between Oct 3, 2018, and Jan 7, 2022, 551 patients were randomly assigned to atezolizumab (n=362) or placebo (n=189). Two patients in the atezolizumab group were excluded from all analyses due to lack of consent. Median follow-up was 28·3 months (IQR 21·2–37·6). 81 (23%) patients in the atezolizumab group and 44 (23%) patients in the placebo group had dMMR disease by central assessment. In the dMMR population, median progression-free survival was not estimable (95% CI 12·4 months–not estimable [NE]) in the atezolizumab group and 6·9 months (6·3–10·1) in the placebo group (hazard ratio [HR] 0·36, 95% CI 0·23–0·57; p=0·0005). In the overall population, median progression-free survival was 10·1 months (95% CI 9·5–12·3) in the atezolizumab group and 8·9 months (8·1–9·6) in the placebo group (HR 0·74, 95% CI 0·61–0·91; p=0·022). Median overall survival was 38·7 months (95% CI 30·6–NE) in the atezolizumab group and 30·2 months (25·0–37·2) in the placebo group (HR 0·82, 95% CI 0·63–1·07; log-rank p=0·048). The p value for the interim analysis of overall survival did not cross the stopping boundary; therefore, the trial will continue until the required number of events are recorded. The most common grade 3–4 adverse events were neutropenia (97 [27%] of 356 patients in the atezolizumab group vs 51 [28%] of 185 in the placebo group) and anaemia (49 [14%] vs 24 [13%]). Treatment-related serious adverse events occurred in 46 (13%) patients in the atezolizumab group and six (3%) patients in the placebo group. Treatment-related deaths occurred in two patients (pneumonia in one patient in each group). Atezolizumab plus chemotherapy increased progression-free survival in patients with advanced or recurrent endometrial carcinoma, particularly in those with dMMR carcinomas, suggesting the addition of atezolizumab to standard chemotherapy as first-line treatment in this specific subgroup. F Hoffmann-La Roche.

Introduction In patients affected by epithelial ovarian cancer (EOC) complete cytoreduction (CC) has been associated with higher survival outcomes. Artificial intelligence (AI) systems have proved clinical benefice in different areas of healthcare. Objective To systematically assemble and analyze the available literature on the use of AI in patients affected by EOC to evaluate its applicability to predict CC compared to traditional statistics. Material and Methods Data search was carried out through PubMed, Scopus, Ovid MEDLINE, Cochrane Library, EMBASE, international congresses and clinical trials. The main search terms were: Artificial Intelligence AND surgery/cytoreduction AND ovarian cancer. Two authors independently performed the search by October 2022 and evaluated the eligibility criteria. Studies were included when data about Artificial Intelligence and methodological data were detailed. Results A total of 1899 cases were analyzed. Survival data were reported in 2 articles: 92% of 5-years overall survival (OS) and 73% of 2-years OS. The median area under the curve (AUC) resulted 0,62. The model accuracy for surgical resection reported in two articles reported was 77,7% and 65,8% respectively while the median AUC was 0,81. On average 8 variables were inserted in the algorithms. The most used parameters were age and Ca125. Discussion AI revealed greater accuracy compared against the logistic regression models data. Survival predictive accuracy and AUC were lower for advanced ovarian cancers. One study analyzed the importance of factors predicting CC in recurrent epithelial ovarian cancer and disease free interval, retroperitoneal recurrence, residual disease at primary surgery and stage represented the main influencing factors. Surgical Complexity Scores resulted to be more useful in the algorithms than pre-operating imaging. Conclusion AI showed better prognostic accuracy if compared to conventional algorithms. However further studies are needed to compare the impact of different AI methods and variables and to provide survival informations.

ObjectiveTo evaluate a wide range of clinical and ultrasound characteristics of different uterine smooth muscle tumors to identify features capable of discriminating between these types.MethodsThis was a retrospective, multicenter study that included 285 patients diagnosed with uterine smooth muscle tumors (50 leiomyosarcomas, 35 smooth muscle tumors of uncertain malignant potential, and 200 leiomyomas). The patients were divided into three groups based on the histological type of their tumors, and the groups were compared according to the variables collected.ResultsLeiomyosarcomas were more common in older and post-menopausal women. Compared with leiomyomas, smooth muscle tumors of uncertain malignant potential and leiomyosarcomas had similar ultrasound features such as absence of normal myometrium, multilocular appearance, hyper-echogenicity in case of uniform echogenicity, absence of posterior shadows, echogenic areas, and hyperechoic rim. Leiomyosarcomas were larger, had more cystic areas, and were associated with a higher prevalence of pelvic free fluid. Smooth muscle tumors of uncertain malignant potential were characterized by a higher frequency of International Federation of Gynecology and Obstetrics (FIGO) type 6–7, the absence of internal shadows, and, in the case of cystic area, the presence of a regular internal wall. Tumor outline varied among the three histological types. A color score of 1 was typical of leiomyoma, a color score 2 was mainly observed in leiomyomas and smooth muscle tumors of uncertain malignant potential, a color score 3 did not differ among the tumors, while a color of score 4 was related to leiomyosarcomas. When combining color scores 3 and 4, leiomyosarcomas and smooth muscle tumors of uncertain malignant potential showed a high percentage of both circumferential and intra-lesional vascularization. A cooked appearance was not statistically different among the tumors.ConclusionsBased on our findings, specific ultrasonographic features as well as age and menopausal status are associated with different uterine smooth muscle tumor types. Integration of these data can help the pre-operative assessment of these lesions for proper management.

ERAS (Enhanced Recovery After Surgery) is a perioperative program combining multiple evidence-based interventions designed to reduce the surgical stress response. Despite the publication of dedicated guidelines, ERAS application to gynecologic surgery outside clinical studies has been slow and fragmented. To promote the systematic adoption of the ERAS program in the entire regional hospital network in Piedmont an Audit-and-Feedback approach (A&F) has been adopted within a cluster randomized controlled trial, aiming to estimate the true impact of the protocol on a large, unselected population. The study protocol provides for a multicenter stepped wedge cluster randomized trial, focused on women undergoing an hysterectomy, for comparison between standard perioperative management and perioperative management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: post-operative complications, quality-of-recovery at 24-hours after surgery, 30-day readmissions, patients' satisfaction, healthcare costs. The compliance to all the ERAS items is monitored with an A&F approach. All the gynecologic units of Piedmont hospitals are involved and all the patients hospitalized for elective hysterectomy in the period of the study are included. Centers, stratified by surgical volume and randomly assigned to four groups, are randomly ordered to activate the ERAS protocol in four periods, every three months. The planned calendar and the total duration of the study have been extended for six months due to the COVID-19 pandemic. The expected sample size of about 2400 patients has a high statistical power (99%) to detect a reduction of LOS of 1 day (effect size 0.5) and to estimate clinically meaningful changes in the other study endpoints. The study protocol has been approved by the Ethical Committee of all participating centers. Study results will be timely circulated within the hospital network and published in peer-reviewed journals. Trial registration

Introduction/BackgroundThe audit-and-feedback (A&F) approach is a key component of the perioperative protocol ERAS (Enhanced Recovery After Surgery) that is often neglected in practice. Few studies evaluated the effectiveness of implementing the ERAS protocol at the regional level, supported by an intensive A&F approach, with an appropriate cluster-randomised design.MethodologyA multi-center stepped wedge cluster randomised trial was conducted in 23 regional hospitals in Piemonte (Italy). Patients undergoing elective hysterectomy, either for cancer or for benign conditions (other than pelvic floor disorders), were eligible. Gynaecologic units (study clusters), stratified by surgical volume, were randomised into 4 groups that progressively adopted the ERAS protocol every 3 months, after specific training. Primary outcome was length of hospital stay (LOS) (without outliers).ResultsBetween September 2019 and May 2021, 2084 patients were included in the main analysis with an intention-to-treat approach, 1104 (53%) in the control period and 980 (47%) in the ERAS period. Compliance to ERAS protocol increased from 60% to 76%, with an adjusted absolute difference of 13·3 points (95%CI: 11·62; 15·03). The ERAS protocol contributed slightly to reduce mean LOS from 3·5 to 3·2 days, with an adjusted reduction of -0·12 days (95%CI: -0·32; 0·08). No difference was observed in the occurrence of complications.ConclusionImplementation of the ERAS protocol for hysterectomy at the regional level, supported by an A&F approach, resulted in a substantial improvement in compliance. This improvement did not translate into relevant reduction of LOS, possibly due to the negative impact of COVID on hospital performance and above all to the short observation period. This study can serve as a replicable model for adopting a comprehensive A&F intervention to support and evaluate the implementation of ERAS in a large, unselected population such as that of a regional hospital network.DisclosuresThe authors have no disclosures to declare. Funding: This work was supported by the Italian Ministry of Health (NET -2016–02364191) and Regione Piemonte (521-A14000) under the Easy-Net project.

Introduction/BackgroundIn 2009 a regional audit on ovarian cancer treatment was run in the Cancer Care Network of Piemonte and Valle d’Aosta in Italy. High dispersion of patients in many low-volume hospitals was documented and 37.5% of patients received sub-optimal care. We present the re-audit and feedback (A&F) intervention performed in 2017–2020 and its impact on the quality of care.MethodologyEight key recommendations on the initial management of ovarian cancer were selected from international guidelines. Thirteen indicators were used to describe the level of adherence to these recommendations. A global indicator of adherence (GIA) was measured as the mean percentage of compliance across all the indicators. All incident cases of ovarian cancer in the resident population were included in the audit, between May 2017 and September 2020. Data were collected in a web-based database. Multiple feedbacks were provided during the audit. Overall survival was identified as outcome indicator.ResultsAmong 1030 women (236–23% early and 794–77% advanced stage) the pattern of care resulted sub-optimal in about 25% of patients. During the audit, overall adherence improved from 51.3% in the first study semester to 70.4% in the last one (estimated difference +17.7%; 95%CI 12.8–22.7). The largest improvement was evidenced in the diagnostic-staging phase (figure1). Overall survival at 4 years was 87.8% among early and 39.4% among advanced stages. During the follow-up (that included the COVID period), no clear trend in 2-year survival was detected, but each 10% increase in GIA was positively associated with a better 2-year overall survival (HR 0.85; 95%CI 0.80–0.91).ConclusionA&F was effective in improving the quality of care for ovarian cancer in Piemonte, even if a clear trend effect on short-term survival was not evident. This successful experience of A&F can be replicable in other settings and different cancers.DisclosuresThe authors have no disclosures to declare. Funding: This work was supported by the Italian Ministry of Health and the Regione Piemonte as part of the Easy-Net Project, grant number NET-2016–02364191.Abstract 580 Figure 1Adjusted estimated effect (OR) of the study period (180 days) on the adherence (%) to selected recommendations

ObjectivesThis survey assessed the implementation of enhanced recovery after surgery (ERAS) for patients undergoing surgery for advanced ovarian cancer in three European cooperative study groups in Scandinavia, Italy, and Austria. The aim was to evaluate the landscape for future trials on ERAS pathways in ovarian cancer, because high-level evidence for such interventions is lacking.MethodsIn July 2017, a web-based questionnaire (SurveyMonkey Inc, Palo Alto, CA, USA) was sent to centers conducting surgery for advanced ovarian cancer within the Nordic Society of Gynecologic Oncology (NSGO), Mario Negri Gynecologic Oncology Group (MaNGO) and other Italian institutions, and the Association for Gynecologic Oncology Austria (AGO Austria) (n = 100). The survey covered all aspects of an ERAS pathway including surgery, nursing, and anesthesia. We herein report on the survey findings relating to surgery, including nursing care issues; however, anesthesiologic issues will be discussed in a separate report.ResultsThe overall response rate was 62%. Only a third of the centers in Italy and Austria follow a written ERAS protocol compared with 60% of the Scandinavian centers. Only a minority of centers have completely abandoned bowel preparation, with the highest proportion in Scandinavia (36%). Two hours of fasting for fluids before surgery is routinely practiced in Scandinavia and Austria (67–57%, respectively), but not in Italy (5%). Carbohydrate loading is routinely administered only in Scandinavia (67%). Peritoneal drainage is used by 22% routinely and by 61% in cases of bowel resection/lymphadenectomy/peritonectomy. Early feeding with a light diet on day 0 or 1 is the standard of care in Scandinavia and Austria, but not in Italy.ConclusionsThe degree of implementation of ERAS protocols varies across and within cooperative groups. The centralization of ovarian cancer care seems to facilitate standardization of peri-operative protocols. Currently, the high heterogeneity in patterns of care may challenge an international approach to a clinical trial.

Introduction/BackgroundSerum Ca125 level is systematically evaluated during maintenance therapy with PARP inhibitors (PARPi) to early detect an ovarian cancer relapse. This study aimed to evaluate whether HE4 or the Systemic Immune Inflammation Index (SII) can anticipate the relapse diagnosis in this setting, when compared to Ca125 alone.MethodologyData from all the patients who had an ovarian cancer relapse during PARPi therapy at S.Anna Hospital in Torino (2017–2023) were collected prospectively. Ca125, HE4, and the blood count were assessed the day before each cycle of PARPi therapy. SII was estimated as (platelet count × neutrophil count)/lymphocyte count.ResultsAmong 76 patients treated with PARPi, 22 relapses (29%) occurred during PARPi therapy, (7–14-1 during Olaparib-Niraparib-Rucaparib, respectively). In these patients, PARPi were used in 64% as a maintenance therapy after first-line chemotherapy and in 36% as maintenance after second-line chemotherapy. Ca125 was elevated in 90% of the relapses and HE4 in 68%. In 7 patients, HE4 started to rise before Ca125 (with a lead time of 1–12 months) and in 1 patient without Ca125 elevation, HE4 anticipated the diagnosis of relapse. A SII index peak was shown in almost all the relapses (19/22), and in 63% this peak coincided (+/- 2 months) with the first rise of Ca125 and/or HE4ConclusionOur data support the use of both Ca125 and HE4 during maintenance therapy with PARPi and SII index peak seems useful to reinforce the suspicion of a relapse when Ca125 and HE4 start to rise. These data should be confirmed on a larger scale trial.DisclosuresThe authors have no disclosures to declare.

ERAS (Enhanced Recovery After Surgery) is a perioperative program combining multiple evidence-based interventions designed to reduce the surgical stress response. Despite the publication of dedicated guidelines, ERAS application to gynecologic surgery outside clinical studies has been slow and fragmented. To promote the systematic adoption of the ERAS program in the entire regional hospital network in Piedmont an Audit-and-Feedback approach (A&F) has been adopted within a cluster randomized controlled trial, aiming to estimate the true impact of the protocol on a large, unselected population. The study protocol provides for a multicenter stepped wedge cluster randomized trial, focused on women undergoing an hysterectomy, for comparison between standard perioperative management and perioperative management according to the ERAS protocol. The primary outcome is the length of hospital stay (LOS). Secondary outcomes are: post-operative complications, quality-of-recovery at 24-hours after surgery, 30-day readmissions, patients' satisfaction, healthcare costs. The compliance to all the ERAS items is monitored with an A&F approach. All the gynecologic units of Piedmont hospitals are involved and all the patients hospitalized for elective hysterectomy in the period of the study are included. Centers, stratified by surgical volume and randomly assigned to four groups, are randomly ordered to activate the ERAS protocol in four periods, every three months. The planned calendar and the total duration of the study have been extended for six months due to the COVID-19 pandemic. The expected sample size of about 2400 patients has a high statistical power (99%) to detect a reduction of LOS of 1 day (effect size 0.5) and to estimate clinically meaningful changes in the other study endpoints. The study protocol has been approved by the Ethical Committee of all participating centers. Study results will be timely circulated within the hospital network and published in peer-reviewed journals. Results are expected to demonstrate positive clinical outcomes of the ERAS protocol even when its implementation is directed towards an entire regional network of gynecologic units, and not only towards selected and highly motivated centers. NCT04063072.