bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of different materials used for fabrication of fixed free fixed dental prostheses: finite element analysis
Authors: Galal Rami M. , ElHotieby Menatallah M. , Hamza Ghada E. , Eldemery Yosra M. 
Published: June 2024

Abstract
Background
This research assessed three materials to be used in the fabrication of fixed free fixed dental prosthesis using finite element analysis. Total deformation, Von Mises stress maximum amounts and sites on both the bone, and the fixed dental prosthesis body were compared.

Methods
3D finite element model was made for the tested fixed dental prosthesis and a contact scanner was used. A fixed free dental prosthesis was made restoring the maxillary first premolar, where second premolar with first molar were the supporting abutments that were scanned. Porcelain fused to metal, CEREC Tessera (Dentsply Sirona) and Poly-Ether-Ketone-Ketone were assessed as fixed free dental prosthesis materials. Cement thickness was adjusted to 40 microns. 100 N vertical load was applied to the central fossa of the pontic in the model.

Results
The deformations in this study were within the acceptable range except with the PEKK fixed free prosthesis. Tessera showed better results than the porcelain fused to metal as the more elastic modulus allows for absorption of energy from loading.

Conclusions
Purely used PEKK is not recommended for fixed free dental prosthesis. Low stiffness fixed dental prosthesis material helps in transferring low amount of load to the underneath tissues.
Effectiveness of low-viscosity resin infiltration (Icon) on color change of enamel white spot lesions: 1-year follow-up clinical study
Authors: Zaazou Mohamed. H. , Saleh Reham S. , Hassan Shahinaz N. , Abdelnabi Ali , Zaki Zeinab M. , Hamdy Tamer M. , Zaki Dalia Y. , Moharam Lamiaa M. 
Published: June 2024

Abstract
Background
To evaluate the effect of the low-viscosity Icon resin infiltrate application on the color change of white spot enamel lesions (WSLs) over 3-, 6-, and 12-m follow-up periods.

Methods
Ninety-six teeth diagnosis with WSLs using the ICDAS scoring system in 49 participants were assessed for their color change using the Icon resin infiltration technique. The Icon kit was applied to WSLs as instructed by the manufacturer. Icon-Etch (15% hydrofluoric acid) was applied to the lesions for 2 min, and then, it was rinsed off with copious amount of water for 30 s. Then, Icon-Dry (99% ethanol) was applied to the etched lesions for 30-s followed by the application of the Icon resin infiltrate that was light cured for 40 s. Color change assessment was performed using Vita Easyshade V spectrophotometer at baseline and immediately after Icon resin infiltration, then at 3-, 6-, and 12-m follow-up periods. Analysis of the data was performed using the test of repeated measure ANOVA and the paired sample t test.

Results
There was a statistically significant difference in ∆E between the different follow-up periods at immediate, 3-m, 6-m, and 12-m. The highest mean value was found in the immediate follow-up period, while the lowest mean value was found in 12-m follow-up period.

Conclusions
Low-viscosity Icon resin infiltration has the ability for immediate diffusion into the WSLs giving an immediate improvement in the esthetic outcome of the WSLs. However, its long-term outcomes might not be consistent for the color change of the WSLs.
The unexpected complications of the left bundle branch area pacing (LBBAP) maneuver: a case report
Authors: Park Soyoon , Choi Young , Oh Yong-Seog , Kim Sung-Hwan 
Published: June 2024

Abstract
Background
The lead of left bundle branch area pacing (LBBAP) inserted into the muscular septum will make the transvenous lead extraction (TLE) of LBBAP more challenging and because in LBBAP ventricular lead (V lead) should be inserted into the part of the septum, damage to the vessel near the lead could occur. The case reports introduced the complications of LBBAP previously introduced, but not being considered in detail.

Case presentation
The two patients (76-year-old man, 90-year-old man) with a complete atrioventricular block (CAVB) undergoing the LBBAP procedure experienced complications related to the procedure. The complications were abrupt dysfunction of V lead and damage to the septal vein in the process of the procedure, respectively. Fortunately, they were discharged without any other complications.

Conclusions
A deliberate approach for the procedure would be needed as well as successful insertion appropriate for the protocol of LBBAP. And long-term follow-up of complications should be needed.
On-treatment (tx) dynamic circulating tumor DNA changes (∆ctDNA) associated with progression-free survival (PFS) and overall survival (OS) of patients (pts) with HR+/HER2− advanced breast cancer (ABC) in MONALEESA-3 (ML-3).
Authors: Chia Stephen K. L. , Solovieff Nadia , Joshi Mukta , Im Seock-Ah , Bianchi Giulia Valeria , de la Cruz-Merino Luis , Jerusalem Guy Heinrich Maria , Sonke Gabe S. , Nusch Arnd , Beck J. Thaddeus , Slamon Dennis J. , Wang Craig , Zarate Juan Pablo , Su Fei , Neven Patrick 
Published: June 2024

1012 Background: In ML-3, ribociclib (RIB) demonstrated a significant PFS/OS benefit over placebo (PBO) in pts with HR+/HER2− ABC. We report associations of on-tx ∆ctDNA with OS/PFS and tumor size and of ctDNA detectability with radiological progression. Methods: Pts were randomized 2:1 to RIB or PBO + fulvestrant as 1st- or 2nd-line tx. ctDNA levels were measured by NGS at cycle 1 day 1 (C1D1), C4D1, C8D1, and every 8 cycles until end of tx. Analyses included: Wilcoxon rank sum text to compare ∆ctDNA from C1D1 to C4D1; Kaplan-Meier method to visualize relationship of ctDNA with PFS/OS; Cox proportional hazards model for associations of ctDNA and tumor metrics (objective response rate, best % change, % change at 1st tumor evaluation); Fisher’s exact test to compare ctDNA detectability between arms; and ∆ctDNA across time points to assess lead time between ctDNA level-based and radiological progression. Results: Overall, 534/726 (73.6%) pts had paired C1/C4 measurements. Rates of detectable (+) and undetectable (−) ctDNA at C1 and C4 were: C1+/C4+, 33.0%; C1+/C4−, 34.5%; C1−/C4−, 27.5%; and C1−/C4+, 5.1%. RIB vs PBO had a larger % decrease in ctDNA level from C1 to C4 (P=0.003). Pts with better best overall response also had larger ctDNA decreases from C1 to C4 (P<0.0001). On-tx ∆ctDNA from C1 to C4 correlated with PFS/OS (P<0.0001; Table). C1-/C4-, C1+/C4-, and C1+/C4+ strongly correlated with PFS within response categories (PR, SD, NCRNPD). C1-to-C4 % ∆ctDNA was only moderately correlated with tumor size change (best % change, r=0.41; change at 1st evaluation, r=0.32; both P<0.001). Univariate/multivariate analyses showed significant correlations between ctDNA metrics (% change, detection pattern at C4D1) and PFS/OS. ctDNA detection and % change generally remained significantly associated with PFS/OS even after adjusting for change in tumor size. In a longitudinal analysis of pts who cleared ctDNA at C4D1 (C4–), the median lead time between ctDNA progression and radiological progression was 8.2 mo (IQR 4.5–15.6). Conclusions: On-tx ∆ctDNA from C1 to C4 was correlated with PFS/OS even after adjusting for tumor size changes, suggesting that ctDNA and tumor dynamics capture distinct aspects of tumor tx responses. Decreases in ctDNA were greater with RIB vs PBO, mirroring ML-3 efficacy readouts but at a much earlier timepoint. This longitudinal analysis of ctDNA in ML-3 suggests that detecting ∆ctDNA is a sensitive way to monitor progression and may be a potential surrogate for efficacy in HR+/HER2− ABC. Clinical trial information: NCT02422615 . [Table: see text]
Real world experience of trastuzumab deruxtecan for the treatment of metastatic breast cancer in the UK.
Authors: Cheng Andy , Frank Suzanne , Baines Katherine , Nathan Mark , Douglas Rosalie V. , Sylva Rushan , Ball Jessica , Savva Constantinos , Talbot Thomas , Oikonomidou Olga , Smith Jenny , Thomson Alastair , Ross Felicity , Konstantis Apostolos , Ainsworth Nicola , Luciano Pietro , Iyer Pooja , Acharige Shyamika , Rana Shaikh , King Judy 
Published: June 2024

1024 Background: Trastuzumab deruxtecan (TDXd), an antibody drug conjugate, was first approved in the UK for the treatment of human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) in 2021. We aimed to review the efficacy and tolerability of TDXd in a real-world UK setting. Methods: We collected clinical and demographic data from medical records on HER2+ mBC patients treated with TDXd in the UK from Jan 2021 to Dec 2023 inclusive. This included: radiological response, the frequency of dose reductions and treatment delays, and reasons for discontinuation. Clinical trial patients were excluded. Descriptive statistical techniques were applied. Results: Data was collected from 26 UK cancer centres on 280 patients. The median age at TDXd initiation was 56 years (range 29-85). Median treatment duration was 9 cycles (range 1-40). 239 patients (85%) had visceral disease. 257 and 196 patients (92% and 70%, respectively) had received prior Trastuzumab and Pertuzumab, respectively. 233 patients (83%) had received prior TDM1. The median number of lines of treatment prior to TDXd was 3 (range 1 to 9). 20 patients (7%) were initiated on a reduced dose and 115 further patients (41%) required at least one dose reduction. 151 patients (54%) had at least one dose interruption due to: infection or neutropenia (n=61), other toxicity (n=85), interstitial lung disease (ILD) investigation (n=39), patient request (n=81), other concurrent illness (n=10), and cardiac investigation (n=6). Of these, 55 patients had more than one treatment break. 157 patients (56%) had discontinued TDXd treatment due to: disease progression or death (n=100), drug toxicity (n=39) of which 22 were due to ILD, and patient choice (n=8). 123 patients remained treatment at the time of analysis. The overall response rate of TDXd was 63% overall: stable disease 23%, partial response 56%, complete response 7%. Conclusions: The real-world data set is not directly comparable to either the DB02 or DB03 trials, as it included patients who had received TDXd in both the second line and later line settings. However, the majority (80%) of these patients were treated in the third line and beyond. The rates of drug interruption and reduction were higher in the real-world data set than in DB02, which may impact on efficacy in the real-world setting. Overall response rate is similar between trial data and our real-world data, although the latter was not measured by RECIST. Data collection is ongoing, including an analysis of real-world progression free survival. [Table: see text]
Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Updated survival results of DESTINY-Breast03.
Authors: Hamilton Erika P. , Hurvitz Sara A. , Im Seock-Ah , Iwata Hiroji , Curigliano Giuseppe , Kim Sung-Bae , Chiu Joanne Wing-Yan , Pedrini Jose Luiz , Li Wei , Yonemori Kan , Bianchini Giampaolo , Loi Sherene , Santos Borges Giuliano , Wang Xian , Bachelot Thomas , Nakatani Shunsuke , Ashfaque Shahid , Liang Zhengkang , Egorov Anton , Cortes Javier 
Published: June 2024

1025 Background: DESTINY-Breast03 (NCT03529110), a randomized, multicenter, open-label, phase 3 study, assessed the efficacy and safety of T-DXd vs T-DM1 in pts with HER2+ mBC treated with ≥1 prior anti-HER2 regimen. Median (m) overall survival (OS) was not reached in either arm at the prior data cutoff (DCO; Jul 25, 2022). We report updated survival results, including efficacy and safety, after median duration of follow-up of 41 mo. Methods: Pts were randomized 1:1 to T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg once every 3 weeks. Primary endpoint was progression-free survival (PFS) by blinded independent central review (assessed at prior DCO); key secondary endpoint was OS. Other secondary endpoints included objective response rate (ORR), PFS, duration of response (DoR), PFS from time of randomization to progression on next line of therapy or death (PFS2), and safety. All secondary endpoints were based on investigator assessment. Results: 524 pts were randomized (T-DXd, n = 261; T-DM1, n = 263). As of Nov 20, 2023, median duration of follow-up was 43.0 mo (range, 0.0-62.9) for T-DXd and 35.4 mo (range, 0.0-60.9) for T-DM1. mOS (95% CI) was 52.6 mo (48.7-not evaluable [NE]) for T-DXd and 42.7 mo (35.4-NE) for T-DM1 (hazard ratio [HR], 0.73), with 110 (42.1%) and 126 (47.9%) OS events, respectively. OS rate (95% CI) at 36 mo was 67.6% (61.3-73.0%; T-DXd) vs 55.7% (49.2-61.7%; T-DM1). mPFS was 29.0 mo for T-DXd and 7.2 mo for T-DM1; PFS rate (95% CI) at 24 mo was 55.8% (49.1-62.0%; T-DXd) vs 20.6% (15.4-26.4%; T-DM1). mPFS2 was 45.2 mo (T-DXd) vs 23.1 mo (T-DM1). Median treatment duration was 18.2 mo (range, 0.7-56.6) with T-DXd vs 6.9 mo (range, 0.7-55.2) with T-DM1; rates of treatment-emergent adverse events (TEAEs) were consistent with prior DCO. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 16.7% of pts with T-DXd (4 new events [all grade 2] since prior DCO) vs 3.4% with T-DM1 (1 new event [grade 1]); neither arm had grade 4 or 5 events. Key efficacy and safety results are shown in the table. Conclusions: The superiority of T-DXd over T-DM1 was reinforced in this long-term analysis, as observed by clinically meaningful improvement in OS, PFS, and PFS2, consistent with prior DCO. The safety profile of T-DXd continues to be manageable with no cumulative toxicities observed with longer follow-up. Clinical trial information: NCT03529110 . [Table: see text]
Survival outcome prediction of breast carcinomas on whole-slide histopathology images using deep learning.
Authors: Paul Julian , Bossard Céline , Rynkiewicz Joseph , Molinié Florence , Salhi Sanae , Frenel Jean-Sebastien , Salhi Yahia , Chetritt Jérôme 
Published: June 2024

1070 Background: Breast cancer is the most common cancer among women with 2 million new cases and 627,000 deaths in 2020. Early diagnosis and effective treatment are crucial for improved outcomes. Prognosis mainly depends on histopathological features, among them grade. As whole slide histopathology image (WSI) of tumor tissue contains a huge amount of hidden morphological features unexploited by pathologists, we investigate the potential of Artificial Intelligence (AI)-based analysis on WSI to predict prognosis in terms of 5-year overall survival in breast cancer patients. Methods: We used a novel deep neural network (DNN), DiaDeepBreastPRS, designed specifically for predicting a survival risk score in breast cancer patients based on H&E-stained whole slide images (WSI) of tumor tissues. The model incorporates two distinct viewpoints, one capturing cellular details and the other the tissue-level information. DiaDeepBreastPRS was trained and evaluated on a multi-centric discovery cohort of 1,027 patients (1,095 H&E WSI) from the TCGA-BRCA dataset using a cross-testing and cross-validation technique. It was evaluated on an external cohort, comprising 232 patients (247 H&E WSI). A statistical analysis with a multivariate Cox regression model was carried out on clinico-pathological data. AI scores and the concordance index (c-index) serves as the metric for assessing the performance. The predicted risk scores were used for effective risk stratification of breast carcinomas. Results: On the TCGA-BRCA dataset, the model achieved an average c-index of 67%, which reaches 78% by adding the pTNM stage and age at diagnosis. On the external dataset, the model achieved a c-index of 66% and 75% when including some histopathological prognosis factors (pTNM stage, age at diagnosis, HER2 and HR status and mitosis). The AI score was independently associated with the survival of breast cancer patients with the highest hazard ratio (HR 2.46, p<0.005). Furthermore, the model was able to significantly discriminate between the 2 groups of patients, with a good and a poor prognosis in terms of overall survival (p<0.005). Conclusions: In this study, we showcased that the algorithm was able to instantly extract prognostic morphological features from H&E whole slide images (WSI) and could be included in the pathology report. This could potentially enhance clinical decision-making, elevating the standard of care. Compared to commonly used molecular signatures, the AI algorithm enables a reduction in response time and cost savings. However, further investigations using additional independent cohorts are essential to consolidate the algorithm's performance and allow its generalizability, establish its superiority over existing prognostic markers, and provide insights into its interpretability.
Real-world (RW) elacestrant use patterns and therapeutic outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC).
Authors: Lloyd Maxwell Roger , Ali Azka , Weipert Caroline M. , Solomon Sheila R , Saha Jayati , Lipsyc-Sharf Marla , Hamilton Erika P. , Kalinsky Kevin , Bardia Aditya , Zhang Nicole , Wander Seth Andrew 
Published: June 2024

1071 Background: Elacestrant was the first novel endocrine therapy (ET) to receive FDA approval in over two decades. In the EMERALD study, pts with ESR1-mutant ( ESR1m) HR+/HER2-negative aBC had a median progression free survival (PFS) of 3.8 months (mos). Here, we use a large clinical-genomic database to assess the RW use of elacestrant and examine the impact of line of therapy (LOT) and number of ERS1m on pt outcomes. Methods: Pts with HR+/HER2- aBC were identified via the GuardantINFORM database; all pts with ESR1m detected on circulating tumor DNA (ctDNA) testing done in routine clinical care and treated with elacestrant after the FDA approval date were included. Real-world time to treatment discontinuation (TTD) and time to next treatment (TTNT) were used as proxies for PFS (measured in mos). For TTD/TTNT, Kaplan-Meier curves and median time-to-event with 95% confidence intervals (CI) were used. For outcomes specific to single versus >1 ESR1m, only pts with an ESR1m detected within the 6 months prior to elacestrant start were included. Results: 418 aBC pts were treated with elacestrant, with a median age of 62 years. Elacestrant was used across metastatic LOT (2nd: 12%, 3rd: 18%, 4tH: 17%, 5th+: 53%). Considering all prior therapies, pts commonly received prior aromatase inhibitors (AI) (89%), CDK4/6i (73%), fulvestrant (63%), and chemotherapy (49%). Of 312 pts with testing within 6 months of elacestrant start, 56% harbored a single ESR1m, with a maximum of 11 ESR1m detected in a single patient. TTD was 5.4 mos (95% CI: 4.2 - not reached [NR]) and TTNT was 6.2 mos (95% CI: 5.7 - NR); most pts were censored at the time of analysis (65% for TTD, 71% for TTNT). There were no significant differences in TTD or TTNT based on number of prior LOT or number of ESR1m mutations (Table 1). Data was not yet mature to assess differences in outcomes based on prior ET use, duration of prior CDK4/6i exposure, specific ESR1m, or co-occurring alterations. Conclusions: Using a clinical-genomic database, we present early RW insights of aBC pts treated with elacestrant. Initial outcomes, as assessed via TTD and TTNT, exceed the PFS reported in the EMERALD trial, perhaps due to multiple factors impacting patient selection and restaging protocols, which can differ in prospective trials versus routine clinical care. Factors such as prior LOT and number of ESR1m did not impact patient outcomes; additional factors such as prior ET use, duration of CDK4/6i treatment, specific ESR1m, and co-occurring mutations will be assessed as data matures. [Table: see text]
Impact of use of antibody drug conjugates on the prognostic outcome of patients with HR+ve/HER2-ve MBC: Results from a real world dataset.
Authors: Dawood Shaheenah S. , Hernández Gema , Segovia Alba 
Published: June 2024

1076 Background: Two antibody drug conjugates trastuzumab deruxtecan (T-DXd - in the HER2 low cohort) and sacituzumab govitecan (SG) have been shown to improve both PFS and OS among pts with HER-ve MBC. The objective of this retrospective analysis was to look at trends in the use of and associated prognostic outcome associated with T-DXd and SG among pts with HR+ve/HER2-ve MBC in the real-world setting. Methods: We utilized a federated network of de-identified health data representing approximately 107 million pt lives available through the TriNetX Research Network. We identified pts with HR+ve/HER2-ve MBC diagnosed between Jan 2004 and Jan 2024. Propensity score matching analysis by age, site of metastases and chemotherapy was carried. OS was computed using the Kaplan Meier product limit method. Results: 17,133 pts with HR+ve/HER2-ve MBC treated with endocrine therapy and CDK4/6i were identified of whom 249 pts (1.45%) and 162 pts (0.94%) received SG and T-DXd respectively. 32 pts (0.19%) received T-DXd + SG. Median time from diagnosis of MBC to start of SG and T-DXd was 625 days and 233 days respectively. 5-yr OS for the whole cohort was 58.1%. 5-yr OS among pts who did and did not receive T-DXd was 74.8% and 52.2% respectively (HR 0.44, 95% CI 0.28 - 0.69; p = 0.0002). 5-yr OS among pts who did and did not receive SG was 73.4% and 64.7% respectively (HR 0.62 95% CI 0.42 - 0.90, p=0.012). 5-yr OS among pts who did and did not receive T-DXd + SG was 77.4% and 62.4% respectively (HR 0.55, 95% CI 0.19 - 1.59, p=0.26). 5-yr OS was 68.1% and 74.5% among pts who had received SG alone or T-DXd alone respectively (HR 1.31, 95% CI 0.84 - 2.03, p =0.22). Conclusions: In a real-world data set we report on the OS benefit associated with the use of SG and/or T-DXd at some time point in the therapy of pts with HR+ve/HER2-ve breast cancer who have progressed on endocrine therapy and CDK4/6i.