bluuebunny/crossref_metadata_2025_split huggingface dataset:
Four-year outcomes and circulating tumor DNA (ctDNA) analysis of pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in unresectable, locally advanced, stage III non–small-cell lung cancer (NSCLC): From KEYNOTE-799.
Authors: Reck Martin , Lee Ki Hyeong , Frost Nikolaj , Breder Valeriy Vladimirovich , Kowalski Dariusz M. , Levchenko Evgeny , Reguart Noemi , Martinez-Marti Alex , Houghton Baerin , Paoli Jean-Baptiste , Safina Sufiia , Liu Hong , Novinskiy Vladimir , Dettman E.J. , Kobie Julie , Jabbour Salma K. 
Published: June 2024

8057 Background: The nonrandomized phase 2 KEYNOTE-799 study (NCT03631784) of pembro + cCRT in previously untreated unresectable, locally advanced, stage III NSCLC demonstrated an ORR of 70.5% in cohort A (squamous and nonsquamous) and 70.6% in cohort B (nonsquamous only) after median follow-up of 18.5 mo and 13.7 mo, respectively. We present outcomes with ⁓4 y of follow-up and analysis of ctDNA. Methods: Eligible patients (pts) were aged ≥18 y with unresectable confirmed stage IIIA–C NSCLC (per AJCC v8), measurable disease per RECIST v1.1, and ECOG PS 0 or 1. Pts in cohort A (squamous and nonsquamous) received carboplatin + paclitaxel and pembro 200 mg for one 3-wk cycle, followed by carboplatin + paclitaxel QW for 6 wks + 2 cycles of pembro 200 mg Q3W + standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin, pemetrexed, and pembro 200 mg Q3W + standard TRT in cycles 2 and 3. All pts received 14 additional cycles of pembro. Primary endpoints were ORR per RECIST v1.1 by BICR and incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). As an exploratory endpoint, tumor ctDNA was assessed in available plasma samples collected at baseline and cycle 7 using the Signatera ctDNA assay. Results: Of 214 pts enrolled, including 112 in cohort A and 102 in cohort B. Median (range) time from first dose to database cutoff (Oct 16, 2023) was 54.1 (49.2–59.4) and 49.3 (38.4–59.1) mo, respectively. ORR was 71.4% in cohort A and 74.5% in cohort B (Table). Grade ≥3 pneumonitis (primary endpoint) occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3–5 treatment-related AEs occurred in 73 pts (65.2%) in cohort A and 52 (51.0%) in cohort B. Of ~136 samples sent for sequencing, 73 pts (~53.7%) had samples evaluable for ctDNA at baseline. ORR was 68.7% in pts with ctDNA detectable (n = 67) vs 50.0% in pts with ctDNA non-detectable samples (n = 6) at baseline. Among 46 pts with ctDNA detectable at baseline and evaluated at cycle 7, 32 (69.6%) had cleared ctDNA at cycle 7; these pts had better trends in PFS and OS vs pts who had not cleared ctDNA at cycle 7 (n = 14). Conclusions: With ~4 y of follow-up, pembro + cCRT continues to demonstrate durable antitumor activity and manageable safety in previously untreated unresectable, locally advanced stage III NSCLC. ctDNA was evaluable in ~half of the samples assessed; most pts with detectable ctDNA at baseline had cleared ctDNA at cycle 7. Clinical trial information: NCT03631784 . [Table: see text]
Clinical outcomes of maintenance durvalumab after definitive concurrent chemoradiotherapy in unresectable locally advanced stage III non-small cell lung cancer according to epidermal growth factor receptor and anaplastic lymphoma kinase status: Korean Cancer Study Group LU-22-18.
Authors: Choi Dae-Ho , Ahn Myung-Ju , Kim Miso , Kim Young Saing , Park Keon Uk , Cho Jang Ho , Kim Hongsik , Lee Ki Hyeong , Ahn Heejoon , Kim Il-Hwan , Lee Kyung-Hee , Lee Gyeong-Won , YI Seong Yoon , AHN Beung Chul , Lee Min-Young , Jung Hyun Ae , Park Sehhoon , Sun Jong-Mu , Ahn Jin Seok , Lee Se-Hoon 
Published: June 2024

8061 Background: The role of maintenance durvalumab after definitive concurrent chemoradiotherapy (CCRT) in unresectable locally advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) mutation or anaplastic lymphoma kinase ( ALK) translocation remains unclear. We compared the effectiveness of durvalumab maintenance therapy in groups with EGFR/ALK wild-type versus those with EGFRor ALK mutations. Methods: In this retrospective multicenter observational study, patients with locally advanced NSCLC without progression after CCRT followed by maintenance durvalumab and available molecular test results ( EGFR and ALK) were eligible. The primary objective was to compare progression-free survival (PFS) between EGFR/ ALK wild-type and EGFRor ALKmutant NSCLC. Secondary objectives include overall survival according to EGFRor ALK mutation and programmed cell death-ligand 1 (PD-L1) expression. Results: Among 339 patients, 279 had wild-type EGFR/ALK, 41 had EGFR mutations and 19 had ALK translocations. The median age was 68 years with 276 males (81.4%) and 63 females (18.6%), 165 (49.3%) had adenocarcinoma, 149 (44.5%) had squamous cell carcinoma, and 21 (6.3%) had other histological types, 120 (35.4%) had stage IIIA, 168 (49.6%) stage IIIB, and 51 (15.0%) had stage IIIC. The majority of patients (n=288, 85%) achieved partial response to CCRT, 2 (0.6%) had a complete response, and 49 patients (14.4%) had stable disease. Excluding 4 patients with unknown PD-L1 tumor proportion score (TPS), 16 (4.8%) had a PD-L1 TPS of 0, 168 (50.1%) had 1-49, and 151 (45.1%) had 50 or higher. The median PFS was 21.4 months (95% CI 17.3–25.3) for the EGFR/ ALK wild-type group and 21.0 months (95% CI 15.7–NA) for the EGFR or ALK mutant group with no significant difference (p=0.74). Significant differences occurred in PFS based on PD-L1 expression with values of 13.6 (95% CI 10.5–NA), 18.7 (95% CI 15.1–26.9), and 24.7 (95% CI 20.7–NA) months for TPS of 0, 1–49, and 50 or higher, respectively (p=0.02). Conclusions: Durvalumab maintenance therapy after definitive CCRT in unresectable locally advanced NSCLC patients with EGFRor ALK mutation demonstrates comparable clinical outcomes to those with wild-type EGFR/ALK when PD-L1 expression is present.
Comprehensive analysis of the value of dynamic changes in ctDNA in SCLC.
Authors: Joseph Peronne , Chen Zhengyi , Ajay Abhishek , Fu Pingfu , Dowlati Afshin 
Published: June 2024

8107 Background: Dynamic changes in circulating tumor DNA (ctDNA) have not been studied in small-cell lung cancer (SCLC). Here, we assessed the changes of ctDNA over time and clinical outcomes. Methods: We performed a 105-gene, hybrid-capture, next-generation sequencing (NGS) liquid biopsy assay that detects SNVs, in/dels, CNVs, and chromosomal rearrangements. Patients had ctDNA assessed at 3 time points: 1) before initiation of front-line therapy; 2) at remission (within 3-6 weeks of 4th cycle of chemotherapy+/- immunotherapy), and 3) at the time of relapse (based on radiographic imaging). Study outcome measures include OS, PFS, DFS (duration of response from completion of 4th cycle of systemic treatment until relapse), and overall response rate (ORR). Survivor distribution was estimated using Kaplan-Meier methods. Cox model was also used to estimate the effects on OS, PFS and DFS. The effects of predictors on ORR were estimated using logistic regression. The T-test was used to examine the difference in continuous measures between the two groups, and the chi-square test was used to examine the association between two categorical factors. All tests were two-sided, and p-values < 0.05 were considered significant. Results: 62 patients were enrolled. The median follow-up was 12.3 mos. Patients were treated with standard-of-care chemotherapy +/- immunotherapy for 4 cycles. 71% had extensive stage disease. At baseline, 100% of patients had detectable variant alleles in TP53,and 70% had variant RB1. Patients with ES-SCLC had significantly higher maximum (max) Variant Allelic Fraction (VAF) (alteration with highest VAF) compared to LS-SCLC (59.1 vs 27.2%, p = 0.04). Median max VAF at baseline was 52.3%, 0.3% at remission, and 38.4% at relapse, indicating a response to therapy. However, ORR did not correlate with baseline max VAF (p = 0.2). Baseline max VAF (comparing those < or > VAF of 45%) was not associated with OS (19.4 vs 12.2 mos, p = 0.6) but highly impacted PFS (11.2 vs. 6.1 mos, p = 0.02) and DFS (12.1 vs 2.2 mos, p = 0.004). Baseline max VAF was an independent predictor of PFS and DFS. A drop in max VAF from pretreatment to remission (comparing those with a > or < 99% decrease) also did not associate with OS, PFS, or DFS. Patients with RB1 alterations at pretreatment that had residual RB1 alterations at the time of clinical remission had significantly worse PFS (6.3 vs 12.1 mos) and DFS (1 vs 8 mos, p = 0.02). Conclusions: Baseline max VAF ctDNA levels strongly correlate with PFS and DFS (duration of remission from completion of 4th cycle of treatment) but not OS and ORR. Most strikingly, those with detectable residual RB1 alterations at completion of proscribed chemotherapy have an extremely short DFS of 1 month that justifies early assessment for clinical trials. This approach has led to a near 90% success rate in enrollment on 2nd line clinical trials or SOC options.
Efficacy and safety of vebreltinib in patients with advanced NSCLC harboring MET exon 14-skipping: Results of 2.5-year follow-up in KUNPENG.
Authors: Yang Jin-Ji , Zhang Yan , Wu Lin , Hu Jie , Wang Zhe-Hai , Chen Jing-Hua , Fan Yun , Lin Gen , Wang Qiming , Yao Yu , Zhao Jun , Chen Yuan , Fang Jian , Song Yong , Zhang Wei , Cheng Ying , Guo Ren-Hua , Li XingYa , Wu Yi-Long 
Published: June 2024

8557 Background: Vebreltinib (PLB1001), a potent and highly selective c-MET inhibitor, demonstrated superior objective response rate (ORR) benefits in locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients (pts) with MET exon 14 (METex14) skipping mutations in the previous analysis of the phase II KUPENG study. Here we present results from 2.5 years of follow-up of pts in KUNPENG. Methods: In this Phase Ⅱ, open-label, multicenter, and multi-cohort study, tumor tissue was assessed for METex14 skipping mutation using next-generation sequencing (NGS) from CAP or CLIA certificated local or central laboratories. Pts in Cohort 1 received 200 mg of vebreltinib twice daily (28 days per cycle) until discontinuation criteria were met. The primary endpoint was ORR assessed by blinded independent review committee (BIRC). Results: Between Jan 17, 2020 and Feb 09,2021, 52 pts were enrolled in Cohort 1. As of the data cutoff date (Aug 09, 2023), the median duration of follow-up was 19.1 months (range, 1.0-42.7) and the median duration of treatment was 9.9 months (range, 0.6-42.7). Per BIRC assessment, the ORR was 75% (95% CI: 61.1-86.0), the disease control rate (DCR) was 96.2% (95% CI 86.8-99.5), the median duration of response (DoR) was 16.5 months (95% CI 9.2-19.4), the median time to response (TTR) was 1.0 month (95% CI 1.0-2.8), the median progression-free survival (PFS) was 14.3 months (95% CI 6.4-18.2), and the median overall survival (OS) was 20.3 months (95% CI 16.2-29.7). The 3-year OS rate was 35.1%. Subgroup analyses showed the ORR was 100.0%, 66.7%, 85.7% and 100.0% among pts with any baseline brain metastases (N=5), pts with any baseline liver metastases (N=6), pts aged 75 years and older (N=21) and pts with co-occurring of MET amplification (N=12), respectively. The most common (≥20%) treatment-related adverse events (TRAEs) in all the 135 pts enrolled in this study were peripheral edema (56.3%), hypoalbuminemia (27.4%), hypoproteinemia (25.9%) and anemia (20.7%). TRAEs were mainly grade 1 or 2. No new safety signals were reported with long-term vebreltinib treatment. Conclusions: Vebreltinib consistently showed promising efficacy and favorable safety in NSCLC pts with METex14 mutations. Clinical trial information: NCT04258033 . [Table: see text]
Precision medicine in NSCLC: Challenges and practice gaps in community cancer clinics.
Authors: Sidiropoulos Nikoletta , Brahmer Julie R. , Storey Janet , Dewald Ilona , Dooyema Samuel , Carter Jeffrey D. , Heggen Cherilyn , McKinnon Kelly E. 
Published: June 2024

8589 Background: Current guidelines for clinical management of advanced NSCLC recommend testing for nine molecular alterations in addition to PD-L1, to identify appropriate patients for targeted therapies. This quality improvement initiative evaluated current practice patterns in biomarker testing in NSCLC in community oncology clinics. Methods: In 2023, 68 healthcare providers (HCPs) from 6 clinics completed surveys on biomarker testing, treatment decision making, and patient-centered care in NSCLC. Teams from each clinic (N=98) then participated in audit/feedback (AF) sessions to assess site-specific gaps and develop and implement action plans for improvement. Results: Many advanced NSCLC patients did not receive the recommended biomarker tests (Table). This is likely related to low rates of next-generation sequencing (NGS) based testing: only 45% or 30% of patients received DNA-based or RNA-based NGS, respectively. Most HCPs (72%) reported testing at time of diagnosis, and about one-third also tested at time of disease progression. However, 48% of HCPs were very/extremely likely to start treatment before receiving molecular test results, and 49% said that "determining whether to begin treatment prior to receipt of molecular testing results" was their top challenge in NSCLC care. Rates of targeted therapy receipt were low, with 33% of HCPs reporting that fewer than half of their patients with an actionable mutation received the corresponding agent. Providers believed "improved collaboration across interprofessional teams" (24%) and "integration of multidisciplinary tumor boards into treatment planning" (22%) would most improve care for NSCLC patients. To address identified gaps, teams developed action plans, including establishing new workflows to better incorporate molecular testing and designating a team member to facilitate multidisciplinary collaboration. Following the AF session, providers reported high confidence in selecting appropriate biomarker tests (83%) and biomarker-directed therapies (75%) for patients with NSCLC . Full findings will be presented, along with follow-up surveys measuring real-world impact of the system-level practice changes. Conclusions: Although most HCPs used some form of molecular testing in NSCLC, testing was not as comprehensive as current guidelines recommend. Through this QI initiative, teams identified gaps/barriers in their own practices, and developed and implemented action plans for improvement. These data and actionable insights support effective and evidence-based integration of biomarker testing in advanced NSCLC to optimize patient outcomes that can help inform improvement strategies for NSCLC care teams in community settings nationwide. [Table: see text]
High Prevalence of Hypercalcitoninemia in a Large Cohort of Adult and Pediatric Patients With PTH Resistance Syndromes
Authors: Cremaschi Arianna , Del Sindaco Giulia , Pagnano Angela , Dolci Alessia , Berkenou Jugurtha , Rothenbuhler Anya , Contarino Andrea , Ferrante Emanuele , Arosio Maura , Giannetta Elisa , Linglart Agnès , Mantovani Giovanna 
Published: June 2024

Abstract

Context
Pseudohypoparathyroidism (PHP) refers to a group of rare hereditary disorders associated with resistance to parathyroid hormone (PTH) and other hormones now termed inactivating PTH/PTHrP disorders (iPPSD). Hypercalcitoninemia has been seldom reported in small series.

Objective
Our aim was to investigate the characteristics of hypercalcitoninemia in pediatric and adult patients with PHP/iPPSD.

Methods
We retrospectively collected data from 2 cohorts from 2 European endocrinology tertiary centers: the pediatric cohort comprised 88 children with available calcitonin (CT) measurements; the adult cohort included 43 individuals with simultaneous CT and PTH measurements.

Results
In the pediatric cohort, 65.9% had hypercalcitoninemia (median CT 15 ng/L); in the adult cohort 53.5% (mean CT 21.6 ng/L). There was no difference between CT in pediatric and adult population; we observed stable CT levels over a median follow-up of 134.5 months in adults. Notably, no correlations were detected between CT and PTH levels. Other etiologies of hypercalcitoninemia were excluded; adult patients underwent regular thyroid ultrasound to screen for medullary thyroid cancer (MTC). We performed 20 calcium stimulation tests in adult patients. While there was a significant difference in basal and peak CT between our patients, healthy subjects, and subjects with MTC, there was no difference with patients with C-cell hyperplasia.

Conclusion
This study underscores the common occurrence of hypercalcitoninemia in both pediatric and adult patients with PHP/iPPSD, in particular with subtypes iPPSD2 and iPPSD3. Furthermore, these patients show hyperresponsiveness to calcium stimulation tests falling between healthy subjects and patients with MTC. These findings contribute to the understanding of CT dynamics in the context of PHP/iPPSD.
Simple prerequisite of presequence for mitochondrial protein import in the unicellular red alga Cyanidioschyzon merolae
Authors: Hirata Riko , Mogi Yuko , Takahashi Kohei , Nozaki Hisayoshi , Higashiyama Tetsuya , Yoshida Yamato 
Published: June 2024

ABSTRACT
Mitochondrial biogenesis relies on hundreds of proteins that are derived from genes encoded in the nucleus. According to the characteristic properties of N-terminal targeting peptides (TPs) and multi-step authentication by the protein translocase called the TOM complex, nascent polypeptides satisfying the requirements are imported into mitochondria. However, it is unknown whether eukaryotic cells with a single mitochondrion per cell have a similar complexity of presequence requirements for mitochondrial protein import compared to other eukaryotes with multiple mitochondria. Based on putative mitochondrial TP sequences in the unicellular red alga Cyanidioschyzon merolae, we designed synthetic TPs and showed that functional TPs must have at least one basic residue and a specific amino acid composition, although their physicochemical properties are not strictly determined. Combined with the simple composition of the TOM complex in C. merolae, our results suggest that a regional positive charge in TPs is verified solely by TOM22 for mitochondrial protein import in C. merolae. The simple authentication mechanism indicates that the monomitochondrial C. merolae does not need to increase the cryptographic complexity of the lock-and-key mechanism for mitochondrial protein import.
Establishing Convergence of Infinite-Server Queues with Batch Arrivals to Shot-Noise Processes
Authors: Daw Andrew , Fralix Brian , Pender Jamol 
Published: June 2024

Stronger Connections and Uncovered Nuance for Queues with Batch Arrivals Many modern queueing systems face the challenge that arrivals occur in batches of customers or jobs. Such simultaneity in the arrival stream may place a particularly acute stress on the service system. Recently, researchers have identified that shot-noise processes, a family of stochastic models for which the dynamics are deterministic between arrival epochs, can be used to approximate batch-arrival queues as justified through batch scaling limits. In “Establishing Convergence of Infinite-Server Queues with Batch Arrivals to Shot-Noise Processes,” Daw, Fralix, and Pender both elevate and generalize these limits, moving from point-wise convergence in distribution for Markovian models to almost sure convergence on a process level (uniformly on compact sets) for general arrival and service processes, allowing for possible nonstationarity and dependence between arrivals. Additionally, the authors establish these batch-scaling limits for both the queue-length and workload processes, and this leads to an unexpected insight. By comparison with the Markovian case, in which the queue-length and workload limits are proportionally identical, for general service distributions, the batch-scaled queue-length and workload processes can differ significantly, revealing that the workload can persist even as the queue length dwindles.
The Gender Disclosure Gap: Salary History Bans Unravel When Men Volunteer Their Income
Authors: Cowgill Bo , Agan Amanda , Gee Laura K. 
Published: June 2024

This study investigates whether the success of salary history bans could be limited by job-seekers volunteering their salaries unprompted. We survey American workers in 2019 and 2021 about their recent job searches, distinguishing when candidates were asked about salary history from when they were not. Historically well-paid workers may have an incentive to disclose, and employers who are aware of this could infer that nondisclosing workers are concealing low salaries. Through this mechanism, all workers could face pressure to avoid the stigma of silence. Our data shows a large percentage of workers (28%) volunteer salary history, even when a ban prevents employers from asking. An additional 47% will disclose if enough other job candidates disclose. Men are more likely than women to disclose their salaries unprompted, especially if they believe other candidates are disclosing. Over our 1.5-year sample covering jurisdictions with (and without) bans, unprompted volunteering of salary histories increased by about 6–8 percentage points. Funding: This work was supported by W.E. Upjohn Institute for Employment Research; Ewing Marion Kauffman Foundation (Emerging Scholars Program). Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2023.17384 .
Mid-term clinical outcomes of the uncemented Robert Mathys pressfit cup
Authors: Ramsodit Kishan Ritek , Sierevelt Inger N , Janssen Esther R C , Kaarsemaker Sjoerd , Haverkamp Daniël 
Published: June 2024

BACKGROUND
The use of uncemented cups during total hip arthroplasty (THA) has gained popularity in recent years. The Robert Mathys (RM) pressfit cup, an uncemented monoblock implant is expected to preserve bone density due to its composition and external surface, while reducing backside wear with its monoblock construction. These factors should lead to a high survival rate of the implant.
AIM
To evaluate the mid-term survival and functional outcome of the RM Pressfit cup in a large study population.
METHODS
Between 2011 and 2020, we included 1324 patients receiving a primary THA using the RM pressfit cup. Final clinical follow-up was performed at 2 years postoperatively with the Dutch arthroplasty register used to assess implant status thereafter. Revision for acetabular failure and reason for revision were reported to evaluate implant survival, while the hip disability and osteoarthritis outcome score (HOOS) scores were used to assess functional outcome.
RESULTS
The mean age at surgery was 64.9 years. The mean follow-up was 4.6 years. Of the 1324 THAs performed, 13 needed cup revisions within 5 years after index THA: 5 due to aseptic loosening, 6 due to infection, 2 due to dislocation and 2 due to other causes. This resulted in a 5-year cup survival of 98.8% (95%CI: 98.1-99.5). Nine of the cup revisions occurred within the first year after index THA. HOOS scores increased significantly in all domains during the first year and levelled out during the second year.
CONCLUSION
In the present study, the RM pressfit cup demonstrated excellent clinical outcomes at mid-term follow-up; however, future studies are needed to assess the long-term outcomes of this acetabular implant.