bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune-related adverse events in patients treated with immunotherapy according to corticosteroid exposure.
Authors: Meraz-Brenez Andres , Aranda-Gutierrez Alejandro , Soliz Dhylan Jael , Reyes-Vanegas Diego , Gonzalez-Sanchez Hector Raul , Martinez-Cannon Bertha Alejandra , Verduzco-Aguirre Haydee Cristina 
Published: June 2024

e14709 Background: Patients with cancer require treatment with corticosteroids for multiple reasons, including prevention of chemotherapy-related side effects. Although corticosteroid use has been associated with lower efficacy of immune checkpoint inhibitors (ICI) in some studies, whether corticosteroid exposure affects the presence and severity of immune-related adverse events (irAEs) remains unclear. Methods: Retrospective single-center study of patients diagnosed with solid tumors treated with ICI. Eligible patients were those who received at least one cycle of ICI and had at least 1 month of follow-up post-ICI initiation. Patient data were extracted from electronic medical records. Comparisons between groups were made based on steroid exposure (defined as the administration of >10 mg of prednisone or its equivalent for >10 days within a 30-day period or at any point during ICI treatment, excluding steroid treatment for irAEs). Associations between variables were assessed using independent samples T-test, Chi-square, and Fisher’s exact tests. Results: We included 135 patients (mean age 61 years, SD 13); 72 (54%) were male. Forty-two (31%) had been exposed to steroids (mean prednisone equivalent of 427 mg, SD 298). Most patients received ICI as palliative treatment for advanced disease (105/135; 78%), primarily as first-line therapy (79/105; 75%). Patients exposed to corticosteroids were more likely to have received ICI with chemotherapy (76% vs 1%, p<0.001), were younger (56 vs. 63 years, p=0.009), more likely to be female (62% vs. 39, p=0.014), and had lower median Charlson Comorbidity Index scores (2 vs. 3, p=0.026). Steroid-exposed patients were more likely to have employed ICI in the neoadjuvant or adjuvant settings (36 vs. 16%, p=0.024) or as third or subsequent line therapy (26 vs. 8%, p=0.044). There were no statistically significant differences in the frequency of irAEs of any grade based on steroid exposure (31% vs 41%, p=0.252). However, patients who were exposed to steroids were significantly less likely to delay or suspend ICI (10% vs. 32%, p=0.005). No other parameters were associated with the rate or severity of irAEs. Conclusions: Our findings suggest that corticosteroid exposure does not increase the frequency of irAEs in patients treated with ICI, but it is associated with a reduced likelihood of discontinuing ICI due to irAEs. These observations suggest that corticosteroids may play a beneficial role in managing patients undergoing immunotherapy, particularly in sustaining treatment continuity despite irAEs. This study underscores the need for further investigation into optimal steroid use strategies to enhance patient outcomes with immunotherapy, especially in situations when they are commonly prescribed, such as premedication for chemotherapy.
FS-1502 in patients with HER2 high expression, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: An open-label, multicenter, phase II study.
Authors: Pan Hongming , Yuan Xiang-lin , Zheng Yu , Peng Hui , Qiu Hong , Wang Jufeng , Li Zhiwei , Gao Shegan , Niu Zuoxing , Yang Jianwei , He Yifu , Wu Guowu , Yu Yiyi , Jieer Ying , Wang Yusheng , Li Zhen , Bai Jun , Liu Huilong , Wu Zhuli , Wang Xingli 
Published: June 2024

e15000 Background: FS-1502 is an antibody-drug conjugate composed of an anti-HER2 antibody, linker, and Monomethylauristatin F. In this study, we conducted an open-label, multicenter, two-cohort phase II trial to evaluate the efficacy and safety of FS-1502 in HER2- positive locally advanced or metastatic gastric or gastroesophageal junction cancer. Methods: Pts with HER2-positive (IHC 3+ or 2+/FISH+) who had received ≥1 prior treatment regimens were eligible and received FS-1502 2.3 mg/kg alone every 3 weeks. The study consists of Cohort 1 for pts received ≥2 lines of previous therapy and Cohort 2 for pts only received first-line of previous therapy, respectively. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression free survival (PFS), overall survival (OS), duration of response, disease control rate, and safety. Results: At data cutoff (Dec 24,2023), 46 pts were enrolled (intent-to-treat [ITT]), 35 pts were confirmed HER2-positive (IHC 3+ or IHC 2+/ISH+, Efficacy Evaluable Set [ES]) by central laboratory. In the ES, the median age was 58.3 years, 48.6% were IHC3+ and primary tumor location in 77.1% of pts was GC. 45.7% (16/35) pts had assigned to cohort 1 and 54.3% (19/35) pts had assigned to cohort 2. In cohort 1, median study follow-up time was 10.1 months, the investigator-assessed ORR was 37.5% (95% CI, 15.2-64.6), median PFS and OS were 4.3 months (95% CI, 1.5-5.8 months) and 10.0 months (95% CI,5.1-NA months), respectively. In cohort 2, median study follow-up time was 12.5 months, the investigator-assessed ORR was 52.6% (95% CI, 28.9-75.6). PFS and OS were 4.4 months (95% CI, 3.0-7.3 months) and 14.6 months (95% CI, 8.7-NA months), respectively. Grade≥3 treatment-related TEAEs were reported in 12 (26.1%) pts, ≥5% were hypokalemia (6.5%) and fatigue(6.5%). No adverse events leading to drug discontinuation or death. Efficacy and safety data are shown in table. Conclusions: FS-1502 showed promising activity with tolerable and manageable safety profile, which warrants further development in HER2-postive, advanced gastric or gastroesophageal junction adenocarcinoma who had received ≥1 prior treatment regimens. [Table: see text]
Disitamab vedotin combined with fruquintinib in patients with HER2-expressing or HER2 mutation/amplified metastatic colorectal cancer refractory to at least two standard regimens: A prospective, exploratory, single-arm study.
Authors: Xu Hui , Peng Jin , Wu Han , Yang Lei , Wang Wenbo , Wang You , Long Xin , He Linli , Zhou Fuxiang 
Published: June 2024

e15003 Background: Human epidermal receptor growth factor 2 (HER2) -expressing or amplified has been identified in 2-6% of patients with stage 3/4 colorectal cancer (CRC), and is associated with poor prognosis, however there are currently no approved HER2-targeted therapies for CRC in China. Herein, we aimed to study the antitumor activity and safety of Disitamab vedotin (RC48), a novel humanized anti-HER2 antibody conjugated to MMAE via a cleavable linker, combined with fruquintinib in patients with HER2-expressing or -amplified metastatic colorectal cancer. Methods: In this prospective, exploratory, single-arm study, patients diagnosed pathologically with mCRC, 18-75 years old harboring HER2 expression or HER2 mutation/amplification, and received at least two lines of treatment. HER2 expression was defined as a score of 1+, 2+ or 3+ on immunohistochemical [IHC] analysis, or mutation/amplification by NGS. Patients received RC48 2.5mg/kg intravenously every 2 weeks. Meanwhile, fruquintinib 3mg was administered orally once daily on days until disease progression, death, intolerable toxicity, withdrawal of consent. The primary endpoint was objective response rate (ORR) per RECIST v1.1; the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: A total of 12 patients were enrolled from November 25, 2022 to June 6, 2023. The results of baseline molecular profiling revealed 4 with IHC 1+, 4 with IHC 2+, 2 with IHC 3+, and 2 with HER2 amplification. In the metastatic setting, patients had received a median of 4 (range, 3-6) lines of prior systemic therapy. In the per-protocol set, the investigator-assessed ORR was 18.2% (2/11) and DCR was 90.9% (10/11). Median PFS was 5.5 months (95% CI: 2.7-8.2) and the median OS was 12.3 months (95% CI: 5.3-19.3). During the study process, 11 (91.7%) patients experienced adverse events (AEs), among which, 4 (33.3%) experienced grade 3 treatment-related AEs (TRAEs). The most common grade 3 TRAEs were neutropenia (25%), leukopenia (16.7%), and hypertension (8.3%). Moreover, no grade 4 or 5 TRAEs were observed. In addition, 4 (33.3%) patients experienced a dose reduction. No patients experienced dose interruption or discontinuation due to TRAEs. Conclusions: RC48 combined with fruquintinib has shown promising efficacy and a manageable safety profile for HER2-expressing or -amplified mCRC patients refractory to at least two standard treatment failures. Clinical trial information: NCT05661357 .
Phase 1 study of ZV0203, a first in class pertuzumab ADC, in patients with HER2 positive advanced solid tumors.
Authors: Miao Zhenwei , Lin Fengjuan , Rao Xi , Huang Yong , Wang Feng , LU Yao , Huang Xiuying , Huang Yunsheng 
Published: June 2024

e15004 Background: ZV0203, a first in class (FIC) pertuzumab antibody-drug conjugate (ADC), targets HER2 positive tumor cells with tubulin inhibitor DUO5 as its payload via a stable and protease-cleavable valine-citrulline linker. In preclinical studies, ZV0203 demonstrated superior antitumor activity compared to Kadcyla in multiple tumor cell line xenograft models with no noticeable toxicity. GLP toxicity studies indicated that ZV0203 was well tolerated with an estimated therapeutic index of 35. Methods: This was an open-label, multicenter, phase 1, dose-escalation study in patients (pts) with HER2+ advanced solid tumors. Primary objectives were safety, tolerability and RP2D. Secondary objectives included PK, immunogenicity and preliminary clinical efficacy. ZV0203 was administered intravenously Q3W on a 21-day cycle. An accelerated titration design was used for the 0.3 and 0.6 mg/kg doses, followed by a 3+3 design for 1.2, 1.8, 2.7 and 3.6 mg/kg dose levels. Results: As of January 18, 2024, 15 pts with solid tumors (breast [11], colorectal [2], gastric [1], lung [1]) were enrolled across doses of 0.3-3.6 mg/kg with a median age of 52 years old (range 35-65), of which 9 pts received prior HER2-targeted therapy (trastuzumab ± pertuzumab) and 14 pts completed 21-day DLT assessment (0.3 mg/kg and 0.6 mg/kg [1 each], 1.2 mg/kg, 1.8 mg/kg, 2.7 mg/kg and 3.6mg/kg [3 each]) with no DLT incidence. Treatment-related adverse events (TRAE) occurred in 14 (93.3%) pts. The most frequent TRAEs were corneal epitheliopathy [9], elevated liver enzymes [6], dry eyes [6], neutropenia [4], anemia [4], leukopenia [3], and proteinuria [3], and most were grade 1-2 in severity. 5 pts experienced grade 3 TRAEs: lymphocytopenia (1.8mg/kg [1]) , corneal epitheliopathy (3.6 mg/kg [1]) and blurred vision (2.7 mg/kg [2], 3.6 mg/kg [1]), which were manageable during treatment. No unexpected safety signals were reported. TRAEs led to 13.3% (2/15) treatment discontinuation. Among 14 pts evaluated, 5 pts achieved a best tumor response of PR; 4 pts had SD; 1 pt had Non-CR/Non-PD per RECIST v1.1. Thus, disease control rate was 71.4% (10/14). PK results demonstrated that the PK profile of total antibody was similar to that of ZV0203 ADC, whose systematic exposure increased in a dose-dependent manner and remained stable after repeated administration. Concentration of DUO5 remained scarce, suggesting good stability of ZV0203. Conclusions: ZV0203 was well tolerated and showed clinically encouraging anti-tumor activity in heavily pretreated pts with HER2 positive cancer. Clinical trial information: NCT05423977 .
The role of folate receptor-positive circulating tumor cells in the prognosis analysis of esophageal squamous cell carcinomas.
Authors: Zhou Qiang , He Qiao , Han Yongtao , Wang Dongsheng , Leng Xuefeng 
Published: June 2024

e15026 Background: Patients with ESCC always be discovered at an advanced stage and have a poor prognosis. The Circulating Tumor Cells (CTCs) were investigated for use as a biomarker for diagnosis and assessing the effectiveness of treatment. This study aims to investigate the predictive value of the baseline level of folate receptor-positive circulating tumor cells (FR+CTCs) for disease-free survival (DFS) and overall survival (OS) in patients with esophageal squamous cell carcinomas (ESCC). Methods: A retrospective observational study was conducted from January 2018 to February 2021 and followed up to June 2022 with ESCC patients in Sichuan Cancer Hospital & Institute Esophageal Cancer Case Management Database (SCCH-ECCM Database). Three ml of peripheral blood were obtained from each patient, and FR+CTCs were quantified using ligand-targeted polymerase chain reaction (LT-PCR). Traditional techniques were employed to measure other serum markers. Clinicopathological features were collected from the hospital medical record system, and survival data (DFS and OS) were obtained by outpatient follow-up or phone calls. The correlation between clinicopathological characteristics, survival data, and FR+CTCs was analyzed. Cox regression analysis was used to assess risk factors that might have an impact on DFS and OS. Results: Analysis was conducted on 123 ESCC patients. Of them, 86% were men, and their average age was 62.0. FR+CTCs did not significantly correlate with patient age, sex, albumin, pre-albumin, C-reactive protein (CRP), ferritin, tumor size, grade of differentiation, metastasis of lymph nodes, perineural invasion/vessel invasion, or tumor size (all P>0.05). But for DFS (HR 3.29; 95% CI 1.52-7.15, P=0.003) and OS (HR 3.85; 95% CI 1.53-9.72, P=0.004), preoperative FR+CTCs were an independent prognostic factor. Patients with post-operative FR+CTCs ≥17.42 FU/3ml had a substantially shorter DFS than patients with FR+CTCs < 17.42 FU/3ml (P=0.0012). Patients with FR+CTCs ≥17.42 FU/3ml had a shorter OS than patients with FR+CTCs <17.42 FU/3ml, although the difference was not statistically significant (P=0.51). Conclusions: Patients with ESCC who have elevated FR+CTCs typically have a poorer prognosis. We anticipate that FR+CTCs will be able to guide clinical treatment, assess patient prognosis, and monitor cancer recurrence and metastasis in real-time.
Thioredoxin 1 in blood as a monitoring biomarker for patients with breast cancer post-treatment.
Authors: Kim Young , Ko Hye Mi , Lee Ye Ri , Suh Kyoung Hoon , Kim Je Ryong , Lee Jin Sun 
Published: June 2024

e15041 Background: The spatial and temporal heterogeneity of tumors in breast cancer pose challenges in precision oncology. Although breast imaging during screening has increased tumor detection and reduced mortality rates, it is limited in tracking minimal residual disease after surgery. Consequently, there is a need for liquid biopsy with easy longitudinal sampling to track real-time changes in tumor characteristics during treatment. Existing biomarkers (CA15-3 and CEA) for post-treatment monitoring are unsatisfactory. This study explores the clinical validity and stability of thioredoxin1 (Trx1) in a 54-month longitudinal study, reflecting tumor characteristics during treatment. Methods: Approved by IRB from Chungnam National University Hospital (IRB: 2021-02-003). Fourteen out of the initial 20 BC patients were finally enrolled because pre-surgery samples for the 6 patients excluded were missing. A total of 116 sera were collected before and after surgery at intervals from 6 to 54 months. After isolating the serum, an immunoassay was performed to measure the level of serum Trx1 using the DxMe® BC kit (E&S Healthcare). CA15-3 and CEA levels were measured in paired samples and collected from medical records. The results were retrospectively analyzed along with clinical information, and the profile of Trx1 level change was analyzed for each individual. Results: The blood Trx1 levels in pre-operation BC patients were 20.68±4.44 U/ml (±SD). From 6 months’ post-operation to the 54th month, blood Trx1 levels in patients were consistently low, averaging 5.43±3.34 U/ml (p < 0.0001 compared to pre-op). In contrast, levels of CEA and CA15-3 did not change significantly before and after surgery. The pre-op and post-op AUC for Trx1, CA15-3, and CEA were 0.998 (95% CI: 0.941 to 1.000), 0.599 (95% CI: 0.482 to 0.709), and 0.550 (95% CI: 0.433 to 0.663), respectively. There was no significant difference in the decreasing profile of Trx1 levels over 54 months between different treatment methods. While existing a microscopic difference according to BC characteristics, all post-op values were already below the cut-off value. Regardless of treatment, Trx1 levels decreased to those of normal healthy women after surgery. There were no recurring cases to compare over 54 months. Conclusions: The results of this 54-month post-operation tracking observation revealed a rapid decrease in Trx1 levels in the blood after surgery, which remained consistently downregulated without a statistical association with pathological findings. This suggests that Trx1 is related to the presence of tumor masses rather than the pathological characteristics of the tumor. It is likely that if any treatment causes the removal and suppression of BC, the level of Trx1 is kept low. Besides its already reported ability to detect BC in blood, Trx1 levels have the potential to serve as a monitoring biomarker in the management of BC patients after treatment.
Correlating survival outcomes in patients with advanced prostate cancer with novel hyperpolarized 13C MRI metabolic imaging biomarkers.
Authors: Chen Hsin-Yu , de Kouchkovsky Ivan , Bok Robert A. , Ohliger Michael A. , Wang Zhen J. , Gebrezgiabhier Daniel , Nickles Tanner , Carvajal Lucas E. , Gordon Jeremy W. , Larson Peder E.Z. , Kurhanewicz John , Aggarwal Rahul Raj , Vigneron Daniel B. 
Published: June 2024

e15059 Background: Hyperpolarized 13C (HP 13C) MRI is a novel molecular imaging approach that detects aberrant aerobic metabolism, namely elevated rates of pyruvate-to-lactate conversion (kPL), in patients with advanced malignancies. Higher kPL has been shown to correlate with higher tumor grade among patients with localized prostate cancer (PC). This research sought to evaluate the correlation between kPL and clinical outcome measures in patients with advanced PC. Methods: Patients with metastatic or locally advanced PC (castration sensitive or resistant) were prospectively enrolled at our institution and underwent HP 13C MRI of one or more target lesions identified on prior conventional imaging. Voxelwise kPL values were computed in MATLAB using an inputless two site exchange model. kPL,median was defined as the median kPL value per-patient across all target lesions; kPL,kurtosis measured the tailedness of the kPL distribution per-patient. We retrospectively analyzed progression free survival (PFS) and overall survival (OS) in subgroups divided by metabolic activity below versus above cut-point (kPL,median <0.017 s-1 and ≥ 0.017s-1, respectively). Survival statistics were calculated using the Cox PH model. Results: Sixteen patients (6 with castration-sensitive and 10 with castration-resistant PC) were accrued. With a median follow-up of 22.0 months from the date of MRI, the lower-kPL subgroup had significantly longer median PFS (11.2 vs 0.5 months; p<0.01) and OS (NR vs 18.4 months; p<0.05) compared to the higher-kPL subgroup. By comparison, baseline serum PSA (PFS: p=0.19, OS: p=0.41) and LDH (PFS: p=0.60, OS: p=0.34) did not demonstrate a significant association with clinical outcomes. There was a strong negative correlation between kPL,kurtosis and OS (r = -0.75), and moderate negative correlations between kPL,median and OS (r = -0.45) as well as kPL,max with both PFS (r = -0.48) and OS (r = -0.54). There was no significant kPL,median difference between castration-sensitive and resistant subgroups (0.015±0.011 vs 0.016±0.006 s-1, p>0.8). Conclusions: HP 13C MRI-derived non-invasive metabolic biomarker kPL,median significantly correlated with clinical outcome measures in a retrospective analysis of patients with advanced PC, outperforming established serological prognostic markers PSA and LDH. Limitations include our small sample size, retrospective design, and heterogeneous patient population. Nevertheless, these encouraging preliminary results support further investigation of HP 13C MRI as a prognostic and/or predictive PC biomarker in multi-center prospective imaging trials. [Table: see text]
Development of custom amplicon-based test systems for detecting KRAS, NRAS, and BRAF gene mutations in colorectal cancer using next-generation sequencing (NGS).
Authors: Zhusina Julia , Aksenova Elena , Larionova Kristina , Nikolaeva Anastasiia , Sluchanko Olesya , Vvedensky Andrey , Bazhenova Julia , Pyankov Denis , Korostelev Sergey 
Published: June 2024

e15061 Background: Polymerase chain reaction (PCR)-based mutation diagnostics in colorectal cancer is widely available. However, PCR has limitations in identifying rare mutations and precise mutation coordinates. Targeted sequencing, though promising, often incurs high costs and longer research durations, demanding higher DNA sample quality. Our study demonstrates the benefits of using a customized amplicon test system for diagnosing somatic mutations in tumor tissue, including detecting rare mutations not captured by PCR, requiring less input biomaterial, and similar research costs. Methods: A targeted NGS assay system was developed using region-specific primers for KRAS (exons 2, 3, and 4), NRAS (exons 2, 3, and 4), and BRAF (exon 15). Library preparation involved a three-step PCR process: Target PCR incorporating Illumina overhang adapter sequences, Index PCR introducing multiplexing indices and sequencing adapters, and PCR cleanup using magnetic beads. Sequencing utilized MiSeq v2 reagents with paired 300‐bp reads, generating high-quality, full-length reads. Validation included re-testing known samples. Tumor cell percentages in FFPE specimens were determined, and DNA was extracted using the QIAamp DNA FFPE Tissue Kit. Data analysis utilized proprietary software. Results: Out of 1234 samples, 1133 were tested, with mutations detected in 685 samples (60.45%). KRAS mutations were found in 548 (48.36%), NRAS mutations in 40 (3.5%), and BRAF mutations in 88 (7.7%) samples. Double mutations were observed in 9 samples (0.79%). Data on rare and double mutations are presented in the table. Conclusions: The developed test system accurately identifies essential mutations in colorectal cancer, including rare and potentially clinically significant variants. The required DNA amount ranged from 10 to 30 ng in 5 μl, nearly ten times less than well-known commercial PCR test systems like COBAS (Roche) and therascreen (QIAGEN). The cost of the study is comparable to PCR with a minimum study duration of 4 days. [Table: see text]