bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesizing a realistic seismic training data set incorporating prior geologic patterns and seismic imaging features for supervised convolutional neural network-based intracratonic strike-slip fault detection
Authors: Jing Jiankun , Yan Zhe , Gong Wei , Li Haiying , Zhang Zheng , Gu Hanming 
Published: June 2024

Intracratonic strike-slip faults play a vital role in hydrocarbon migration and accumulation, making their accurate detection crucial for subsurface structure interpretation and reservoir characterization. Although numerous approaches have been developed for automatic fault interpretation, they are still unable to fully recognize intracratonic strike-slip faults with subtle reflection variations in seismic images. We develop a supervised convolutional neural network (CNN) to automatically and precisely delineate these faults in 3D seismic images. The primary obstacle in using a CNN for this task is the lack of diverse seismic training samples and corresponding high-quality labels. To address this, we develop an efficient two-step workflow for automatically generating a tremendous amount of 3D seismic training sample pairs: (1) guided by the prior geologic structure patterns of the study area, we use parameterized vector fields to simulate various velocity models with accurate fault labels incorporating realistic intracratonic strike-slip faulting features, such as the transtensional, transpressional, and strike-slip translational types and (2) following seismic imaging laws, we synthesize seismic training samples from simulated velocity models through the point-spread function-based convolution method. One synthetic and two field examples demonstrate that the CNN trained with this seismic data set containing prior geologic patterns and seismic imaging features outperforms the conventional fault detection approaches in accurately and continuously delineating intracratonic strike-slip faults.
Comparing the somatic, germline, and immune landscapes of upper tract urothelial carcinoma (UTUC) and UC of the bladder (UCB).
Authors: Yuen Kit L. , Meagher Margaret F. , Mercer Jacob , Yilma Binyam , Stoppler Melissa Conrad , Fragkogianni Stamatina , Mar Nataliya , Rezazadeh Arash , Gupta Shilpa , Grivas Petros , Bagrodia Aditya , McKay Rana R. , Stewart Tyler F. , Salmasi Amirali 
Published: June 2024

4520 Background: Molecular characterization of anatomically distinct UCs has been limited by the rarity of UTUC; however, recent advances in real-world data curation have enabled larger UTUC cohort generation. Here, we investigated the somatic, germline, and immunologic landscapes of UTUC compared to UCB. Methods: From the Tempus Database, we retrospectively analyzed de-identified next-generation sequencing data from 505 UTUC (224 ureter, 281 renal pelvis) and 2,416 UCB cases (2,379 bladder, 37 urethra). Tumors were sequenced with the Tempus xT DNA and xR RNA assays. Pathogenic somatic mutations, immune cell infiltration predicted from gene expression patterns, TMB, PD-L1 from IHC, MSI, and mismatch repair (MMR) were evaluated. Incidental germline alterations were assessed in 46 genes for patients with tumor/normal-matched (T/N) sequencing (UTUC n=285, UCB n=1,359). Chi-squared, Fisher's exact, and Wilcoxon rank-sum tests were used to assess statistical significance (p<0.05, q<0.05 for false discovery rate correction for multiple testing). Results: Median age of the UTUC and UCB cohort were 73 and 70 years, respectively (p=0.003). The UCB cohort had significantly more males (75% vs 56%, p<0.001) and ever smokers (59% vs 46%, p<0.001).Alterations in TERT, TP53, CDK12, RB1, ERBB2, and CDKN1A were more frequent in UCB, while KMT2D, FGFR3, BRIP1, CDKN2B, KRAS, and MYC more frequent in UTUC (Table). Additionally, FGFR3 fusions were more frequent in UTUC. Germline variants were found in 7.1% of UCB and 7.0% of UTUC cases, with trends towards higher prevalence of alterations in lynch-associated genes ( MLH1, MSH2, MSH6, PMS2) in UTUC (0.6% vs 1.8%, p=0.059). The prevalence of TMB ≥ 10 mut/Mb was higher in UCB vs UTUC (17% vs 11%, p<0.001). UCB had increased PD-L1 positivity (p=0.013), whereas UTUC had more MSI-high (UTUC = 3.2% vs UCB = 1%, p=0.001) and deficient MMR (p=0.020) cases. There were similar proportions of total immune infiltrates in UCB and UTUC. However, UTUC harbored a higher percentage of CD4+ T cells (p<0.001), while UCB had a higher proportion of regulatory T and NK cells (p<0.001). Conclusions: Via comprehensive molecular characterization of UC, we observed distinct DNA alteration and tumor microenvironment patterns in UTUC and UCB. The germline results underline how T/N testing can identify patients with UTUC and/or UCB who can benefit from dedicated germline testing. Further research is warranted to elucidate the clinical implications of these findings. [Table: see text]
Tumor-specific MHC class II upregulation associated with response to anti-PD-L1 therapy in patients with urothelial cancer.
Authors: Hasakioğulları İlayda , Kockx Mark , Szabados Bernadett , Young Matthew , Powles Thomas 
Published: June 2024

4584 Background: The mechanism of response and resistance to immune checkpoint inhibition (ICI) remains to be defined in urothelial cancer. Methods: The abacus study explored neo-adjuvant atezolizumab prior to cystectomy in muscle-invasive bladder cancer (MIBC, NCT02662309). In this post hoc exploratory analysis, we utilized samples from the Abacus. Nanostring GeoMx Digital Spatial Profiler (DSP), a spatial transcriptomics platform enabling comprehensive characterization of the entire human transcriptome while preserving spatial information, was performed on Formalin Fixed Paraffin Embedded (FFPE) tissue from 12 paired biopsies (3 pCR, 3 MPR, and 6 relapse tumors). To guide region selection and tissue segmentation on the GeoMx DSP, we utilized SYTO 13, PanCK, CD45, and CD3 markers. Subsequently, we quantified the entire transcriptome in selected regions and conducted differential gene expression analysis using the DSP data analysis suite and BioTuring Lens platforms. Results: Tumor cells of the MPR samples showed upregulation of MHC class II genes (log2FC >1.52, q < 5.5E-04, p< 9.7E-07). pCR samples showed numerous tertiary lymphoid structures (TLS) in the remaining tumor bed. We then performed MHC class II (HLA-DR) immunohistochemistry staining to confirm this transcriptome-level finding on available FFPE samples from Abacus. The MPR response group (n=4) had significantly higher levels of MHC class II expression on tumor cells after the treatment than relapse (n=12) and stable disease (n=15) patients ( p < 0.001). Conclusions: Upregulation of MHC class II on tumor cells in anti-PD-L1 responding patients is a novel finding. Together with the TLS presence, they offer insights into potential mechanisms underlying treatment response, thus aiding in identifying predictive biomarkers for ICI therapy in MIBC.
Survival outcomes of small cell variant bladder cancer: Analysis from nationwide study.
Authors: Ganiyani Mohammad Arfat , Khosla Atulya Aman , Ahmad Shahzaib , Jatwani Karan , Bellur Shreyas S , Aziz Nouman , Rubens Muni , Roy Mukesh , Bastos Bruno R. , Ozambela Manuel , Eldefrawy Ahmed , Manoharan Murugesan , Garje Rohan 
Published: June 2024

4606 Background: Small cell carcinoma of bladder (SCB) is a rare and aggressive histological subtype. While the survival impact of various treatment modalities for the classic urothelial bladder cancer has been well-researched, limited studies exists on the survival outcomes of these treatment modalities in patients with SCB, primarily due to the exclusion of these patients from clinical trials. This study aims to explore the impact of different treatment modalities on the survival outcome of patients with SCB using data from a large nationwide registry. Methods: This retrospective study queried the National Cancer Database from 2004 to 2020 and followed STROBE guidelines. The primary analytic cohort included patients diagnosed with locoregional SCB based on the TNM stage (T1-T4, N0-N3, M0). Treatment modalities comprised perioperative systemic therapy combined with definitive surgery (PST), concurrent chemoradiation (CR), surgery only (S), Radiation therapy only (RT) and systemic therapy only (ST). This study utilized Kaplan-Meier survival analysis and the Cox Proportional regression. Results: The study included 4,658 patients with locoregional SCB. The analysis revealed 236 (4.82%) patients with SCB received PST, 752 (15.36%) got CR, 612 (12.50%) underwent S, 3,029 (61.85%) received ST, and 268 (5.47%) had RT. The median overall survival was 64.49 months (CI: 41.4-75.1, P < 0.001) with PST, 29.27 months (CI: 22.9-35.88), with CR, 14.13 months (CI: 9.92-21.65) with S alone, 21.29 months (CI: 18.53-23.69) with ST, and 7.82 months (CI: 6.24-9.53) with RT alone. In the multivariate analysis, combining perioperative systemic therapy with surgery led to a 54% reduction in hazards of death (HR: 0.46; CI: 0.37-0.58) compared to surgery alone, whereas CCR achieved a 41.16% (HR: 0.59; CI: 0.47-0.73) decrease in hazard, illustrating the effectiveness of multimodal treatment for SCB. Conclusions: Treatment approaches with either systemic therapy combined with definitive surgery or concurrent chemoradiation enhanced survival outcomes, highlighting the significance of a multimodal approach for patients with SCB. [Table: see text]
Real-world data based on PD-L1 expression in early-stage NSCLC in an east-Asian patient population: A 10-year follow-up study.
Authors: Hong Ji Hyung , Ko Elaine Yee-Ling , Lee Young Sub , Moon Youngkyu , Kim Seoung Joon , Lecoultre Marc , Shih David Jen-Hao , Lee Victor Ho-Fun , Hui Rina , Hong Sook-Hee , EL Helali Aya 
Published: June 2024

8019 Background: Recent studies on the perioperative treatment of Non-Small Cell Lung Cancer (NSCLC) have often excluded patients with stage IA. To address this issue and bridge the knowledge gap, we aim to investigate the impact of PD-L1 and EGFR status on survival in stage IA NSCLC. Methods: Our study aimed to determine the impact of PD-L1 expression on overall survival (OS) in patients with resectable stage IA-IIIB NSCLC who underwent curative resection between May 2010 and April 2020. We analyzed survival and clinicopathological data and categorized patients based on PD-L1 tumor proportion score (TPS). PD-L1 TPS ≥ 50% were categorized as PD-L1 high and < 50% as PD-L1 negative/low. Our primary objective was to assess the association between PD-L1 expression status and OS in resectable NSCLC patients. We also investigated the relationships between OS, PD-L1 expression, EGFR status, and tumor stage. Results: Among the 386 patients recruited, those with PD-L1 negative/low and high had a 5-year OS of 82% and 63%, respectively ( p = 0.00011). Among patients with stage IA NSCLC, those with PD-L1 negative/low demonstrated the most favorable 5-year OS (96%) compared to the other subgroups (stage IA PD-L1 high 63%, stage IB-IIIB PD-L1 negative/low 67% and stage IB-IIIB PD-L1 high 62%, p < 0.0001). Stage IA EGFR mutant NSCLC showed a significantly better 5-year OS compared to EGFR wildtype (97% versus 84%, p= 0.0028). In comparison, survival in stage IB-IIIB NSCLC was similar regardless of EGFR status (stage IB-IIIB/EGFR mutant 66% vs EGFR wildtype 65%, p= 0.13). Next, we addressed the impact of the co-occurrence of an EGFR mutation and PD-L1 expression on survival in stage IA. In stage IA, the PD-L1 high EGFR mutant and wildtype subgroups demonstrated a 5-year OS of 83% and 56%, respectively, while in the PD-L1 negative/low subgroup, the EGFR mutant and wildtype had a 98% and 93% OS ( p< 0.0001), respectively. Conclusions: Stage IA NSCLC patients with PD-L1 high and EGFR wildtype, surprisingly, were associated with poorer survival outcomes. These findings highlight the urgent need for clinical trials investigating perioperative management strategies in this population.
Surgical outcomes in patients with non-small cell lung cancer receiving neoadjuvant chemoimmunotherapy versus chemotherapy alone: A systematic review and meta-analysis.
Authors: Aburaki Riona , Fujiwara Yu , Chida Kohei , Horita Nobuyuki , Nagasaka Misako 
Published: June 2024

8020 Background: Neoadjuvant immune checkpoint blockade (ICB) including programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) blockade in combination with chemotherapy has been shown to improve survival outcomes in patients with early-stage non-small cell lung cancer (NSCLC). However, its impact on surgery has not been fully elucidated yet. We aimed to compare surgical outcomes between neoadjuvant chemoimmunotherapy with PD-1/PD-L1 blockade and chemotherapy alone in patients with resectable NSCLC. Methods: We performed a systematic search of PubMed and Embase for randomized-controlled trials (RCTs) that compared neoadjuvant chemoimmunotherapy to chemotherapy alone in patients with resectable NSCLC and reported surgical outcomes including surgical resection rates, R0 resection rates, postoperative complications, any-grade treatment-related adverse events (TRAEs), grade 3-5 TRAEs, serious AEs (SAEs), and AEs leading to cancellation of surgery. Meta-analysis was performed using the random-effects model to pool odds ratios (ORs) of these surgical and safety outcomes. Heterogeneity among the included studies for each outcome was assessed using I2 statistics and high heterogeneity was defined as I2 higher than 50%. Results: A systematic review identified 5 RCTs with 2,069 patients for a meta-analysis. All identified RCTs evaluated combination of neoadjuvant PD-1/ PD-L1 blockade with chemotherapy versus chemotherapy alone. Chemoimmunotherapy was associated with an improvement in R0 resection rates (OR 1.72, 95% CI 1.22 - 2.42; p = 0.002), whereas surgical resection rates were comparable between two groups (OR 1.51, 95% CI 0.90 - 2.51; p = 0.12). No significant difference was observed for complication rates, any-grade TRAEs, grade 3-5 TRAEs, SAEs, or AEs leading to cancellation of surgery. (Table). Conclusions: Although the surgical resection rate itself was not significantly different between neoadjuvant chemoimmunotherapy and chemotherapy alone, neoadjuvant chemoimmunotherapy was associated with increased R0 resection rates without an increase in the incidence of complications, TRAEs, and cancellation of surgery. This indicates that neoadjuvant chemoimmunotherapy can be safely administered with an increase in R0 resection rate, which potentially leads to improvement of survival outcomes in patients with resectable NSCLC. [Table: see text]
A phase II study of tislelizumab (TIS) and chemotherapy as neoadjuvant therapy for potentially resectable stage IIIA/IIIB non-small cell lung cancer (NSCLC).
Authors: Wang Ting , Li Lu , Huang Lin , Liu Jie Wei , Zhu Da Xing , Dong Jing Si , Deng Han Yu , Zheng Xi , Tian Long , Jiang Li Li , Wang Wei Ya , Zhou Ping , Su Ming Gang , Pu Dan , Cai Xu Yu , Feng Ming Yang , Ou Xue Jin , Wang Yongsheng , Zhou Qing Hua 
Published: June 2024

8024 Background: Neoadjuvant immunotherapy and chemotherapy provide more surgical opportunities and survival benefits to potentially resectable locally advanced NSCLC remains unclear. Herein, we initiated a phase II study to evaluate the feasibility of neoadjuvant immunotherapy and chemotherapy in stage IIIA/IIIB NSCLC. We report the the updated analysis of the study. Methods: Patients (pts) with stage IIIA/IIIB EGFR/ALK/ROS wild-type NSCLC received 2 cycles of neoadjuvantchemoimmunotherapy (PD-1 inhibitor TIS, nab-paclitaxel, and cisplatin/carboplatin) and were reassessed for surgery.Thereafter, pts underwent surgery within 6 weeks and continued 2 cycles of TIS plus chemotherapy, followed by up to 15 cycles of TIS monotherapy. The primary endpoint was R0 resection rate, and secondary endpoints included major pathologic response (MPR), pathologic complete response (pCR), 1/2-year EFS rate, and overall survival, etc. Results: From Jan 2021 to Sep 2023, 33 pts were enrolled; 19 (58% ) pts with IIIA and 14 (42%) pts with IIIB disease, As of 14 Sep 2023, 27 pts completed neoadjuvant and 25 pts underwent resection. and 6 pts were on neoadjuvant. 2 pts downstaging had obvious downstaging after neoadjuvant treatment and were unwilling to surgery. 24 of 25 pts (96%) underwent successful R0 resection (Table). Of 25 pts who underwent resection,8 (32%) pts achieved pCR, 15 (60%) pts achieved pathologic response rate.Of the 7 pts who achieved MPR, 5 had only about 1% viable tumor cells in the resection specimen. The overall response rate (ORR) and disease control rate (DCR) were 88% (22/25) and 100 % (25/25), respectively. The clinical downstaging occurred in 22 of 25 pts (88%).The pathological downstaging occurred in 23 of 25 pts (92%).And The 1-year EFS rate 82.3% (95%CI 58.3-93.2), 2-year EFS rate 76.4% (95%CI 51.1-89.8). Conclusions: Neoadjuvant TIS plus chemotherapy increased surgical opportunities and survival benefits in potentially resectable locally advanced stage IIIA/IIIB NSCLC. [Table: see text]
Next-generation sequencing (NGS) completion and timeliness using reflex testing protocol for patients with stage II-III non-squamous non-small cell lung cancer (NS-NSCLC).
Authors: Maheshwari Shipra , Smilnak Gordon , Singh Rishika , Williams Eli , Stelow Edward B , Pandey Subodh , Martin Linda , Larner James Mitchell , Hall Richard Delmar , Gentzler Ryan D. 
Published: June 2024

8060 Background: Genomic testing is important for early-stage NSCLC due to benefits of adjuvant EGFR and ALK targeted therapies and implications for neoadjuvant immunotherapy decisions. The purpose of this study is to evaluate the completion rates and timeliness of NGS prior to treatment initiation for patients with stage II-III NS-NSCLC, with reflex NGS testing protocols in place. Methods: Patients with stage II-III NS-NSCLC diagnosed between 2015 and 2022 at UVA Cancer Center were identified retrospectively. A reflex tissue-based NGS testing protocol was initiated at UVA in early 2015 using in-house TruSight Tumor and later PGDx platforms. Targeted pyrosequencing was performed in cases of NGS failures. The primary outcomes of the study were to evaluate the NGS completion rate and median time from biopsy to results and to any first line treatment (1L), including surgery, radiation, or systemic therapy. Actionable mutation incidence, proportion of patients with test results prior to treatment, and overall survival (OS) were all assessed. Statistical analysis included both descriptive statistics and Kaplan-Meier methodology for overall survival (OS). Results: 171 patients met eligibility, 92 (54%) female, 80 (47%) stage II and 91 (53%) stage III. 159 (93%) had known 1L start dates and 99 (58%) received systemic therapy with known dates. Testing completion rates and time to results are shown in the table. Actionable mutations identified included: KRAS 39% (G12C 15%), EGFR 7%, BRAF 4%, MET 2%, RET 1%, and NTRK 1%. There was no difference in NGS success rates between patients with stage II and III diseases, X2 (1, N = 171) = 2.667, p = 0.102. Median OS was 64.1 months in those with complete NGS testing and 53.4 months in those without complete NGS (p=0.222). Conclusions: Reflexive, in-house NGS resulted in a shorter median time from biopsy to results (17 days) and higher completion rate (NGS, 77%; at least limited testing, 92%) compared to historical controls. The majority of patients had NGS results available to inform systemic therapy decisions (69%). While OS was numerically higher for patients with complete NGS, this was not statistically significant. Reflex NGS testing protocols increase the likelihood of obtaining timely results in the new era of adjuvant tyrosine kinase inhibitors and neoadjuvant chemotherapy and immunotherapy. [Table: see text]
Combining SBRT with GM-CSF and Peg-IFNα to induce abscopal effects in previously treated patients with stage IV thymic tumors.
Authors: Fan Min , Wang Boyan , Chen Jiayan , Wen Junmiao , Li Huiting 
Published: June 2024

8112 Background: After the failure of multi-line treatment, patients with stage Ⅳ thymic tumors have a poor prognosis and few therapeutic options. Combining stereotactic body radiotherapy (SBRT) with granulocyte-macrophage colony-stimulating factor (GM-CSF) and Pegylated interferon-α (Peg-IFNα) may induce abscopal effects and improve prognosis. Methods: We conducted this open-label, single-arm, phase Ⅱ trial to evaluate SBRT plus GM-CSF and Peg-IFNα in previously treated patients with stage Ⅳ thymic tumors. A 21-day treatment cycle consisted of SBRT delivered to one metastatic lesion with 30 Gy in 5 fractions from day 1, synchronous subcutaneous injection of GM-CSF 125 μg/ m2 once daily for 14 days, and subcutaneous injection of Peg-IFNα 90 μg on day 8. If the patient has more than two metastatic lesions, another treatment cycle was repeated. After the completion of 1 or 2 treatment cycles, Peg-IFNα therapy was maintained for at least half a year with a subcutaneous injection of 90 μg once a month. The two primary endpoints were the proportion of patients with abscopal effects and the objective response rate (ORR). The secondary endpoints included overall survival (OS), progression-free survival (PFS), and therapeutic safety. Results: A total of 20 patients from March 2021 to September 2022, were enrolled in this trial, with 1 (5.0%) type A thymoma, 2 (10.0%) type B1 thymoma, 2 (10.0%) type B2 thymoma, 1 (5.0%) type B3 thymoma, 12 (60.0%) thymic squamous cell carcinoma and 2 (10.0%) thymic neuroendocrine tumor. At a median follow-up of 18.6 months, 8 (40.0%) out of 20 patients had abscopal effects, and the ORR was 45.0%. The median OS had not been attained yet. The median PFS was 9.0 months. We observed that patients with abscopal effects tended to have longer OS and PFS than those without abscopal effects (Figure 1). 3 patients (15.0%) experienced Grade 3 treatment-related adverse events (CTCAE version 5.0), among which cardiac insufficiency compelled 1 patient (5.0%) to drop out of treatment. Conclusions: Combining SBRT with GM-CSF and Peg-IFNα was well tolerated with acceptable toxicity and may represent a promising salvage therapy for previously treated patients with stage Ⅳ thymic tumors. The occurrence of abscopal effects is likely to improve patient outcomes. Clinical trial information: NCT04517539 .