P–132 Centralized versus local embryologists scoring of blastocyst quality obtained in a large European multicenter clinical trial

Study question Does blastocyst quality scoring by central assessment deviate from local assessment and potentially lead to the selection of a different single blastocyst for transfer? Summary answer Central and local assessment provided the same quality classification (poor / good / top) in 69% of all blastocysts and 63% of all transferred blastocysts. What is known already Blastocyst quality is scored most frequently by three morphological parameters, namely expansion and hatching (EH) status, inner cell mass (ICM) grading and trophectoderm (TE) grading. The score is used to define the quality classification (poor / good / top) which determines which embryo is to be transferred or cryopreserved. Blastocyst scoring and grading can be highly subjective, which does influence the choice for transfer and cryopreservation. Time-lapse imaging technology captures additional input about embryo development as well as enables centralized data storage and sharing for independent central assessments. Study design, size, duration Pooled embryo analysis from a prospective, randomized, multicenter trial (RAINBOW) of 619 women undergoing ovarian stimulation with an individualized dose of follitropin delta in a long GnRH agonist protocol between May 2018 and January 2020. Blastocysts were centrally assessed using time-lapse images by two independent assessors and one adjudicator . Selection of the blastocyst for transfer by local assessment was based on morphological scoring and not on morphokinetic time-lapse parameters. Participants/materials, setting, methods Oocytes were fertilized by ICSI and cultured in the Embryoscopeâ (Vitrolife) up to day 5 for transfer or day 5/6 for cryopreservation. Embryos were assessed as either non-blastocyst or blastocyst. Blastocysts were graded centrally and locally at 116 hrs of development, based on EH status (1–6), ICM (A-D) and TE grading (A-D). Central assessors were blinded to local assessment and embryo transfer selection. Main results and the role of chance In total 4282 embryos were assessed centrally, of which 2046 day 5 embryos (48%) were adjudicated due to a scoring difference of at least one parameter between the two central assessors. In total 38% of day 5 embryos were judged as non-blastocysts and 62% as blastocysts of which 61% (i.e. 38% of all embryos) were determined to be of good or top quality. Identical results in terms of quality classification (poor / good / top) were obtained for 69% of blastocysts between local and central assessment and in 78%, between the two central assessors. Moreover, central and local scoring were identical in 62% for EH status, 53% for ICM grading and 57% for TE grading. For all transferred blastocysts (n = 508), central and local quality assessment was aligned for 63%. The ongoing pregnancy rate following single blastocyst transfer (SBT) was 41% (202/489), and similar to when considering only the transfers for which the central assessment had the same or a higher classification than the local assessment (166/411=40%). In 16% of all SBT, central quality assessment gave a lower score for the transferred blastocyst than the central assessment. This discrepancy could potentially have led to transfer of a different blastocyst. Limitations, reasons for caution This trial included assessments made by embryologists from 20 IVF centres. Some centres has limited experience with time-lapse technology for morphological blastocyst scoring. Scoring could therefore have been affected by differences in focal planes, magnification and contrast compared to inverted microscopy, with potential influence on blastocyst scores and quality classification. Wider implications of the findings: Local and central blastocyst quality classification based on morphology aligns well but remains subjective. Embryo assessment may benefit from using tools like artificial intelligence-based algorithms for a more objective analysis. Trial registration number NCT03564509

Complex System for Earthquake Prediction, Warning and Local Assessment of Seismic Events

A complex system for zonal earthquake prediction, warning, and local assessment of seismic events has been designed, performed, implemented, and experimented/validated. The system was designed to ensure simultaneously: the reception of warning signals following earthquakes with the epicentre on a radius of 1000 km; acquisition of local precursor data for a possible prediction of seismic events with the epicentre in the perimeter of the targeted locality and/or improvement of the database in the field of Earth physics purchased and processed centrally at the national seismic dispatcher; acquisition of data on the intensity of local seismic movements, based on which, when a predetermined threshold considered dangerous is exceeded, a real-time action order is issued for the protection of high-risk equipment and installations in operation. The realized system is structured on the national seismic dispatcher DSN (with the role of seismic data acquisition from the territory) connected by a bidirectional communication system with a local dispatcher DL which is provided with a system for acquiring and storing local seismic data (vibration detector 3D and temperature transducer mounted in a 40 m deep drilled well, radon detector and associated parameters: temperature, pressure, and humidity of the air mounted at the mouth of the drilled well). The implemented system is able, through the specialized software implemented, to take over the warning signals received from the national seismic dispatcher, to process the locally acquired data, and after the local validation of the seismic event to issue real-time action command (when exceeding values of pre-established major risk threshold) of the protections of high-risk installations in operation in the targeted perimeter. The experimentation/validation of the system, of the interconnection networks, and of the specialized software of the implemented application was done both by continuously recording the local seismic parameters, verifying the communication between DSN and DL, and by taking two warnings regarding seismic events produced (on 30.10.2020  Mw = 7, Greece and on 22.10.2020, at 20:22 hours, ML = 4 R, Vrancea, RO). By processing the data recorded during these events, the speeds of seismic waves in the respective directions were calculated. Thus, for the event of 30.10.2020 Greece, a speed of seismic waves of 7,418 km/second was determined and for the event from 22.10.2020 Vrancea, at 20:22 hours, it was calculated that the secondary waves are moving with 12,686 km/second and the surface seismic waves with 5,063 km/second. Following the analysis/comparison of acceleration intensities with the pre-set threshold level recorded locally for potentially dangerous events, it was found that these events were felt in Râmnicu Vâlcea at a level below the pre-set danger threshold and consequently, the specialized software of the application did not generate a control signal for actuating the protection of high-risk equipment in operation.

We couldn’t resist comparing central with local RECIST1.1 and with Choi assessment: Exploratory analysis of tumor imaging in EORTC STBSG Phase 2 trial 1317 “CaboGIST.

e23563 Background: Gastrointestinal stromal tumor (GIST) is commonly driven by activating mutations in KIT or PDGFRA. Advanced GIST is treated with tyrosine kinase inhibitors (TKIs) but develops resistance over time. EORTC 1317 assessed the safety and activity of cabozantinib, a multi-TKI targeting KIT, MET, AXL and proangiogenic pathways, in GIST patients who had progressed on imatinib and sunitinib. The efficacy analysis of the trial, which met its primary endpoint, was based on local assessment of RECIST1.1 response. RECIST neglects myxoid degeneration, necrosis and vascular remodeling induced by TKIs without major volumetric changes. Density changes on CT scans can predict clinical benefit and can be assessed by Choi criteria. Methods: We describe results of a post hoc exploratory analysis of CT scans performed centrally using RECIST 1.1 and Choi criteria. Results: Week 12 scans were available and evaluable by central review in 43 pts, Choi in 42 cases. Comparisons between local and central RECIST1.1 outcome revealed discrepancies in 17/43 evaluable cases (39.5%). When comparing Choi with local and central RECIST1.1 at week 12, discrepancies were observed in 27/42 (64.3%) and 21/42 (50%) evaluable cases, respectively. In summary, 70% of evaluable patients were progression-free and alive at week 12 based on local assessment, 86% and 83% according to central RECIST1.1 and Choi criteria, respectively. The main difference was the rate of objective response with cabozantinib in week 12: 5 PR (12%) with local RECIST1.1, 3 PR (7%) with central assessment, and 21 PR (50%) with Choi criteria. Conclusions: RECIST1.1 remains an unsatisfactory tool for response assessment in GIST, illustrated by the high inter-rater variability of response outcome comparing local versus central analysis. RECIST1.1 clearly underestimates the anti-tumor activity of TKIs in GIST. Cabozantinib did not only meet the primary endpoint of this trial when applying RECIST1.1 per protocol, but achieved objective responses in 50% of evaluable patients in week 12 when using Choi criteria. [Table: see text]