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Background: In an interim analysis of this phase 3 trial, the addition of pembrolizumab to chemotherapy resulted in longer progression-free survival than chemotherapy alone among patients with advanced triple-negative breast cancer whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS; the number of PD-L1-staining tumor cells, lymphocytes, and macrophages, divided by the total number of viable tumor cells, multiplied by 100) of 10 or more. The results of the final analysis of overall survival have not been reported.Methods: We randomly assigned patients with previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer in a 2:1 ratio to receive pembrolizumab (200 mg) every 3 weeks plus the investigator's choice of chemotherapy (nanoparticle albumin-bound paclitaxel, paclitaxel, or gemcitabine-carboplatin) or placebo plus chemotherapy. The primary end points were progression-free survival (reported previously) and overall survival among patients whose tumors expressed PD-L1 with a CPS of 10 or more (the CPS-10 subgroup), among patients whose tumors expressed PD-L1 with a CPS of 1 or more (the CPS-1 subgroup), and in the intention-to-treat population. Safety was also assessed.Results: A total of 847 patients underwent randomization: 566 were assigned to the pembrolizumab-chemotherapy group, and 281 to the placebo-chemotherapy group. The median follow-up was 44.1 months. In the CPS-10 subgroup, the median overall survival was 23.0 months in the pembrolizumab-chemotherapy group and 16.1 months in the placebo-chemotherapy group (hazard ratio for death, 0.73; 95% confidence interval [CI], 0.55 to 0.95; two-sided P = 0.0185 [criterion for significance met]); in the CPS-1 subgroup, the median overall survival was 17.6 and 16.0 months in the two groups, respectively (hazard ratio, 0.86; 95% CI, 0.72 to 1.04; two-sided P = 0.1125 [not significant]); and in the intention-to-treat population, the median overall survival was 17.2 and 15.5 months, respectively (hazard ratio, 0.89; 95% CI, 0.76 to 1.05 [significance not tested]). Adverse events of grade 3, 4, or 5 that were related to the trial regimen occurred in 68.1% of the patients in the pembrolizumab-chemotherapy group and in 66.9% in the placebo-chemotherapy group, including death in 0.4% of the patients in the pembrolizumab-chemotherapy group and in no patients in the placebo-chemotherapy group.Conclusions: Among patients with advanced triple-negative breast cancer whose tumors expressed PD-L1 with a CPS of 10 or more, the addition of pembrolizumab to chemotherapy resulted in significantly longer overall survival than chemotherapy alone. (Funded by Merck Sharp and Dohme; KEYNOTE-355 ClinicalTrials.gov number, NCT02819518.). [ABSTRACT FROM AUTHOR]

Non-clear cell renal cell carcinoma (non-ccRCC) is a highly heterogeneous disease group, accounting for approximately 25% of all RCC cases. Due to its rarity and especially heterogeneity, phase III trial data is limited and treatment options generally follow those of clear cell RCC. In the literature, there exists a number of studies with sunitinib, cabozantinib, and everolimus, but data on the efficacy of pazopanib are limited. Our aim in this study was to compare the efficacy of pazopanib and sunitinib, in a multicenter retrospective cohort of non-ccRCC patients. Our study included patients diagnosed with non-ccRCC who received pazopanib or sunitinib treatment as first-line therapy from 22 tertiary hospitals. We compared the progression-free survival (PFS), overall survival (OS), and response rates of pazopanib and sunitinib treatments. Additionally, we investigated prognostic factors in non-ccRCC. PFS and response rates of sunitinib and pazopanib were found to be similar, while a numerical difference was observed in OS. Being 65 years and older, being in the intermediate or poor risk group according to the International Metastatic Renal Cell Carcinoma Database Consortium, having liver metastases, presence of a sarcomatoid component, and having de novo metastatic disease were found to be significantly associated with shorter PFS. Pazopanib treatment appears to have similar efficacy in the treatment of non-ccRCC compared to sunitinib. Though randomized controlled trials are lacking and will probably be never be available, we suggest that pazopanib could be a preferred agent like sunitinib and cabozantinib.

Purpose: A head-to-head comparison of efficacy between a cyclin-dependent kinase 4/6 inhibitor plus endocrine therapy (ET) versus combination chemotherapy (CT) has never been reported in patients with clinically aggressive hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC)., Methods: In this open-label, multicenter, randomized phase II trial, pre/perimenopausal women with clinically aggressive HR+/HER2- ABC were randomly assigned 1:1 to first-line ribociclib (600 mg once daily; 3 weeks on, 1 week off) plus letrozole/anastrozole and goserelin or investigator's choice of combination CT (docetaxel plus capecitabine, paclitaxel plus gemcitabine, or capecitabine plus vinorelbine). The primary end point was progression-free survival (PFS)., Results: Among 222 patients randomly assigned to ribociclib plus ET (n = 112) or combination CT (n = 110), 150 (67.6%) had symptomatic visceral metastases, 41 (18.5%) had rapid disease progression per investigator's judgment, and 31 (14.0%) had symptomatic nonvisceral disease. Overall, 106 (47.7%) patients had investigator-assessed visceral crisis. The median follow-up time was 37.0 months. At data cutoff, 31.3% (ribociclib arm) and 15.5% (CT arm) of patients had completed study treatment and transitioned to post-trial access. The median PFS was 21.8 months (ribociclib plus ET; [95% CI, 17.4 to 26.7]) and 12.8 months (combination CT; [95% CI, 10.1 to 18.4); hazard ratio, 0.61 [95% CI, 0.43 to 0.87]; P = .003. The overall response rates and the median time to response in the ribociclib versus CT arms, respectively, were 66.1% and 61.8% and 4.9 months and 3.2 months (hazard ratio, 0.76 [95% CI, 0.55 to 1.06]). Lower rates of symptomatic adverse events were observed in the ribociclib versus CT arm., Conclusion: First-line ribociclib plus ET showed a significant PFS benefit, similar response rates, and better tolerability over combination CT in patients with clinically aggressive HR+/HER2- ABC.

Introduction: Decision-making for complex pediatric urinary system stone disease is still a challenge for pediatric urologists. The interest in supine percutaneous nephrolithotomy (PCNL) is increasing among centers to achieve high surgical success rates with less morbidity. Despite advanced retrograde intrarenal surgery armamentarium, percutaneous approaches remain the first-line surgical treatment modality for >2 cm and complex renal stones. There are no comparative studies yet in the literature for pediatric endoscopic combined intrarenal surgery (ECIRS) OBJECTIVE: In this study, we aimed to contribute to the literature by evaluating the safety and efficacy of ECIRS by comparing it with PCNL., Study Design: Patients under 18 years of age who underwent PCNL and ECIRS for urinary tract stone disease at our Pediatric Urology department between 2012 and 2024 were included. Preoperative (demographic characteristics, stone characteristics, biochemical parameters), perioperative (duration of surgery, number of accesses, lasing and fluoroscopy times, endoscopic and fluoroscopic stone-free rates) and postoperative (hospital stay, urinary tract infection, complication and radiological stone-free rates) parameters were retrospectively evaluated., Results: A total of 68 children [28 (41%) girls and 40 (59%) boys] aged 5 (0-17) years were included in the study. ECIRS was performed in 19 (28%), supine in 28 (41%) and prone PCNL in 21 (30%) patients. Age (p = 0.029), Guy's stone score (p < 0.001), S.T.O.N.E. (p < 0.001), and Seoul National University Renal Stone Complexity (S-ReSC) scores (p = 0.001) for preoperative parameters were found to be higher in ECIRS group over both PCNL methods (Summary Table). However, Clinical Research Office of the Endourological Society (CROES) score was seen lower for ECIRS group patients compared to other groups (p = 0.028). Surgery time (in favor of supine over prone PCNL), fluoroscopy time (in favor of ECIRS and Supine PCNL over Prone PCNL), preferred laser type (prone PCNL group was mostly performed with holmium laser, whereas other groups were balanced between Holmium and Thulium Fiber Laser) and exit strategy (the preferred exit strategy was DJ Stent in most of the ECIRS patients, whereas nephrostomy tube was used in some of the PCNL group) showed significant difference among the groups as perioperative parameters (p = 0.042, <0.001, <0.001, <0.001, respectively). Surgery time was lower for supine PCNL compared to prone PCNL. For postoperative parameters, stone-free rates, complication rates and urinary tract infections were similar between the 3 groups, while a difference was detected in terms of length of hospital stay in favor of ECIRS over both supine and prone PCNL (p = 0.006)., Discussion: The current trial suggests that stone-free and complication rates of ECIRS and supine PCNL were similar in the pediatric complex stone patients. Although, the stones in the ECIRS group we found to be more complex. Also, ECIRS was superior to PCNL in terms of fluoroscopy exposure and hospital stay., Conclusion: With the widespread use of new generation ureteral access sheaths and flexible ureterorenoscopes, ECIRS may have an important role in treatment of complex pediatric kidney stones., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

The fact that the human epidermal growth factor receptor 2 (HER2)-low group, historically classified as HER2 negative in breast cancer histology, benefited from HER2-targeted treatments similarly to the HER2-positive group indicates that this group has a distinct histology from the HER2-0 group. The effectiveness of cyclin-dependent kinase 4/6 inhibitors, which are the standard first-line treatment for hormone receptor-positive, HER2-negative advanced breast cancer, in this newly defined histological subgroup remains a topic of debate. In our study, we examined the impact of HER2 status on the efficacy of CDK4/6 inhibitors. Our study is a retrospective, multicenter, real-world data analysis. One hundred sixty patients were included in the study. The relationship between HER2 status and other clinical-pathological features, as well as progression-free survival, was examined. Median follow-up was 20.33 ± 0.98 months. The mPFS could not be reached. All patients exhibited positive estrogen receptor expression. Among the patients, 111 (69.4%) were categorized as HER2-0, and 49 (30.6%) as HER2-low. The 24-month progression-free survival rates were similar between HER2-0 and HER2-low patients (60.6% vs 65.3%, hormone receptor: 1.18, CI: 0.67-2.20, P = .554). We established that the mPFS achieved with cyclin-dependent kinase 4/6 inhibitors as a first-line therapy for patients with advanced breast cancer is unaffected by HER2 status., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC., Methods: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1., Results: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2-14.3) and 10.3 months (2.7-13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2-44.1] and sunitinib/pazopanib (29.2% [18.6-41.8]). Grade 3-5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects., Conclusions: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab., Clinical Trial Registration: ClinicalTrials.gov; NCT03260894 ., (© 2023. The Author(s).)

Background: In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355., Methods: Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30), Breast Cancer-Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline., Results: Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = -1.81, 95% confidence interval [CI] = -6.92 to 3.30), emotional functioning (least-squares mean difference = -1.43, 95% CI = -7.03 to 4.16), physical functioning (least-squares mean difference = -1.05, 95% CI = -6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = -5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning., Conclusions: Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10)., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Metastatic castration-resistant prostate cancer (mCRPC) remains a challenging condition to treat despite recent advancements. This retrospective study aimed to assess the activity and tolerability of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) in mCRPC patients across multiple cancer centers in Turkey. The study included 165 patients who received at least one cycle of Lu-177 PSMA-617 RLT, with the majority having bone metastases and undergone prior treatments. Prostate-specific antigen (PSA) levels were assessed before each treatment cycle, and the biochemical response was evaluated in accordance with the Prostate Cancer Work Group 3 Criteria. The PSA decline of ≥50% was classified as a response, while an increase of ≥25% in PSA levels was indicative of progressive disease. Neither response nor progression was considered as stable disease. The Lu-177 PSMA-617 RLT led to a significant PSA response, with 50.6% of patients achieving a >50% decrease in PSA levels. Median overall survival (OS) and progression-free survival were 13.5 and 8.2 months, respectively. Patients receiving Lu-177 PSMA-617 RLT in combination with androgen receptor pathway inhibitors (ARPIs) had a higher OS compared to those receiving Lu-177 PSMA-617 RLT alone (18.2 vs 12.3 months, P = .265). The treatment was generally well-tolerated, with manageable side effects such as anemia and thrombocytopenia. This study provides real-world evidence supporting the effectiveness and safety of Lu-177 PSMA-617 RLT in mCRPC patients, particularly when used in combination with ARPIs. These findings contribute to the growing body of evidence on the potential benefits of PSMA-targeted therapies in advanced prostate cancer., (© 2023 UICC.)

Background: Immunotherapy-based combinations including pembrolizumab plus lenvatinib are the standard of care for patients with first-line clear-cell renal cell carcinoma, but these combinations are not well characterised in non-clear-cell renal cell carcinoma. We aimed to assess the activity and safety of pembrolizumab plus lenvatinib as a first-line treatment for patients with advanced non-clear-cell renal cell carcinoma., Methods: KEYNOTE-B61 is a single-arm, phase 2 trial being conducted at 48 sites (hospitals and cancer centres) in 14 countries (Australia, Canada, France, Hungary, Ireland, Italy, Poland, South Korea, Russia, Spain, Türkiye, Ukraine, the UK, and the USA). Adult patients (aged ≥18 years) with previously untreated stage IV non-clear-cell renal cell carcinoma and a Karnofsky performance status of 70% or higher were eligible for enrolment. All enrolled patients received pembrolizumab 400 mg intravenously every 6 weeks for up to 18 cycles (2 years) plus lenvatinib 20 mg orally once daily or until disease progression, unacceptable toxicity, or withdrawal; lenvatinib could be continued beyond 2 years. The primary endpoint was the proportion of patients with a confirmed objective response as per adjusted Response Evaluation Criteria in Solid Tumours (version 1.1) assessed by independent central review. Activity and safety were analysed in all patients who received at least one dose of study treatment (the as-treated population). This trial is registered with ClinicalTrials.gov (NCT04704219) and is no longer recruiting participants but is ongoing., Findings: Between Feb 23, 2021, and Jan 21, 2022, 215 patients were screened; 158 were enrolled and received treatment. Median age at baseline was 60 years (IQR 52-69), 112 (71%) of 158 patients were male, 46 (29%) were female, 128 (81%) were White, 12 (8%) were Asian, three (2%) were Black or African American, and 15 (9%) were missing data on race. As of data cutoff (Nov 7, 2022), median study follow-up was 14·9 months (IQR 11·1-17·4). 78 of 158 patients had a confirmed objective response (49%; 95% CI 41-57), including nine (6%) patients with a confirmed complete response and 69 (44%) with a confirmed partial response. Grade 3-4 treatment-related adverse events occurred in 81 (51%) of 158 patients, the most common of which were hypertension (37 [23%] of 158), proteinuria (seven [4%]), and stomatitis (six [4%]). Serious treatment-related adverse events occurred in 31 (20%) of 158 patients. Eight (5%) patients died due to adverse events, none of which was considered related to the treatment by the investigators (one each of cardiac failure, peritonitis, pneumonia, sepsis, cerebrovascular accident, suicide, pneumothorax, and pulmonary embolism)., Interpretation: Pembrolizumab plus lenvatinib has durable antitumour activity in patients with previously untreated advanced non-clear-cell renal cell carcinoma, with a safety profile consistent with that of previous studies. Results from KEYNOTE-B61 support the use of pembrolizumab plus lenvatinib as a first-line treatment option for these patients., Funding: Merck Sharp & Dohme (a subsidiary of Merck & Co, NJ, USA), and Eisai., Competing Interests: Declaration of interests LA reports consulting fees (paid to their institution) from Astellas, Bristol Myers Squibb, Ipsen, Janssen, Merck, MSD, Pfizer, Eisai, and Roche; and travel expenses from Bristol Myers Squibb, MSD, and Ipsen. HG has received honoraria from Pfizer and MSD; and participated on advisory boards for Pfizer, Merck Serono, MSD, Ipsen, Bristol Myers Squibb, and Astellas. CS has received research support from Ipsen; honoraria from Bristol Myers Squibb, Pfizer, Roche, Astellas, Ipsen, Sanofi, Bayer, and MSD; and travel support from Bristol Myers Squibb, Pfizer, Roche, Astellas, Ipsen, Sanofi, Bayer, and MSD. MAC has received honoraria from Bristol Myers Squibb, Roche, MSD, Ipsen, EUSA, AstraZeneca, Merck, Pfizer, Astellas, Janssen, and Bayer; and travel support from Astellas, Janssen, Bayer, Roche, MSD, Merck, and Pfizer. DP has received honoraria from Bayer and Merck/Pfizer; travel support from Merck/Pfizer and Janssen, and participated in advisory boards for Merck/Pfizer, Bristol Myers Squibb, and MSD. PB has received research support from MSD, Bristol Myers Squibb, Ipsen, Pfizer, Merck, AstraZeneca, and Janssen; consulting fees from Bristol Myers Squibb, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Amgen, Gilead, Eisai, and AstraZeneca; honoraria from Bristol Myers Squibb, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, Astellas, Bayer, Novartis, Eisai, and AstraZeneca; travel support from Bristol Myers Squibb, Ipsen, MSD, Merck, Pfizer, Janssen-Cilag, and Astellas; and participated on a data safety monitoring board or advisory board for Orion. JLL has received research support (paid to their institution) from Pfizer, Ipsen, Bristol Myers Squibb, MSD, Merck, Roche, Genentech, AstraZeneca, Amgen, SeaGen, and GI Innovation; participated on a data safety monitoring board or advisory board for Pfizer Korea, Astellas Korea, Bristol Myers Squibb, Merck, MSD, AstraZeneca, Amgen, and GI Innovation; and has stocks in Amgen, Johnson and Johnson, and Merck. VS has received research support from Merck Sharp & Dohme (a subsidiary of Merck & Co, Rahway, NJ, USA); honoraria from Pfizer Export BV, Stada-Ukraine, Kyiv Vitamin Plant, Astellas Pharma, PrJSC Pharmaceutical firm Darnytsia, and Pharma Personal Group Bionorica. TF has received research support from MSD; and travel support from Bayer and MSD. PW has received consulting fees and honoraria from Astellas Pharma and MSD, Bayer, Janssen Cilag, Ipsen, Pfizer, and Merck; travel support from Pfizer; and has participated on advisory boards for Astellas Pharma, MSD, Bayer, Janssen Cilag, Ipsen, Pfizer, and Merck. EG has received honoraria from Eli Lilly, Roche, Pfizer, Novartis, Janssen Oncology, Astellas Pharma, Amgen, AstraZeneca, Bristol Myers Squibb, Gilead Sciences, Sandoz-Novartis, Abdi Ibrahim, MSD Oncology, and Genekor; travel support from Roche, Pfizer, Novartis, Janssen Oncology, Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Sciences, and Abdi Ibrahim; participated on advisory boards for Eli Lilly, Roche, Pfizer, Novartis, AstraZeneca, Bristol Myers Squibb, Gilead Sciences, Sandoz-Novartis, and MSD Oncology; and owns stock in ImmunoGen and MacroGenics. CG has received consulting fees from Cadex Genomics and BCAL Diagnostics, participated on a data safety monitoring board or advisory board for Alloplex Biotherapeutics, and was a member of a scientific advisory committee for Brain Cancer Biobanking Australia, Cooperative Trials Group for Neuro-Oncology, Australian and New Zealand Urogenital and Prostate Cancer Trials Group, Mark Hughes Foundation, and International Kidney Cancer Coalition. RFP, MS, and XP are employees of Merck & Co (Rahway, NJ, USA). C-HL has received research support (paid to institution) from Merck, Eisai, AstraZeneca, Bristol Myers Squibb, Calithera Biosciences, and Exelixis; consulting fees from Aveo, Bristol Myers Squibb, Exelixis, Eisai, Merck, Pfizer, EMD Serono, and Cardinal; honoraria from AiCME, IDEOlogy Health, Intellisphere, MJH Life Sciences, Medscape, and Research to Practice; and is on the medical steering committee for the Kidney Cancer Association. PT, LL, and VA declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)