bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety analysis by treatment periods from EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization with durvalumab with/without bevacizumab in participants with embolization-eligible unresectable hepatocellular carcinoma.
Authors: Kudo Masatoshi , Chan Stephen Lam , Sangro Bruno , Erinjeri Joseph P. , Qin Shukui , Ren Zhenggang , Arai Yasuaki , Breder Valeriy Vladimirovich , Lin Shi-Ming , Peron Jean-Marie , Nguyen Tien Quang , Yan Lunan , Chiu Chang-Fang , Santos Florinda A. , Veluvolu Anil , Thungappa Satheesh Chiradoni , Morgan Claire , Parsons Kerry , Xynos Ioannis , Lencioni Riccardo 
Published: August 2024

65 Background: The global Phase 3 EMERALD-1 study (NCT03778957) primary endpoint was met: durvalumab (D) + bevacizumab (B) + transarterial chemoembolization (TACE) significantly improved progression-free survival vs placebos (pbos) + TACE (median 15.0 vs 8.2 mo; HR, 0.77; 95% CI, 0.61–0.98; p=0.032 [threshold 0.0435]) in participants (pts) with embolization-eligible unresectable hepatocellular carcinoma (uHCC) with a manageable safety profile. This post hoc, exploratory analysis assessed safety in the study’s two treatment (tx) periods (pds): D-TACE (D-T) and D-B. Methods: Pts were randomized 1:1:1 to D+TACE, D+B+TACE, or pbos+TACE. In the D-T pd, pts received 1–4 TACE (cTACE or DEB-TACE [investigator choice]) plus D (1500 mg Q4W) or pbo for D. In the D-B pd, post-last TACE, pts received D (1120 mg Q3W) plus pbo for B, D (1120 mg Q3W) plus B (15 mg/kg Q3W), or pbos for D and B. Adverse events (AEs), start/end date, maximum/change in CTCAE grade, and causality were assessed in the D-T and D-B pds in pts who received any study tx in the arm to which they were randomized, until end of follow-up. Results: The Table shows duration of exposure (DoE). In the D+TACE, D+B+TACE, and pbos+TACE arms, AEs were reported by 144 (74.6%), 139 (72.0%), and 148 (74.0%) pts in the D-T pd and 133 (68.9%), 147 (76.2%), and 132 (66.0%) pts in the D-B pd; were possibly related (pos rel) to study tx in 59 (30.6%), 56 (29.0%), and 41 (20.5%) pts in the D-T pd and 76 (39.4%), 114 (59.1%), and 69 (34.5%) pts in the D-B pd; and were provoked by TACE in 72 (37.3%), 90 (46.6%), and 85 (42.5%) pts in the D-T pd and 16 (8.3%), 18 (9.3%), and 21 (10.5%) pts in the D-B pd, respectively. Conclusions: D+B+TACE had a manageable safety profile across the D-T and D-B pds, consistent with the individual agents and underlying disease. These data further support D+B+TACE as a new potential standard of care in embolization-eligible uHCC. Clinical trial information: NCT03778957 . [Table: see text]
Utility of radiomic features in predicting clinical outcomes in stage II-III pancreatic cancer.
Authors: Itakura Haruka , Xu Qinmei , Toesca Diego , Vitzthum Lucas , Jamalian Arash , Schueler Emil , Alkim Emel , Baclay J Richelcyn , Chang Daniel Tandel , Fisher George A. 
Published: August 2024

74 Background: We identified computed tomography (CT)-derived radiomic features predictive of tumor progression within three months, then examined their ability to prognosticate overall survival (OS) along with clinical features in pancreatic cancer. We evaluated these features in patients with unresected pancreatic cancer who underwent stereotactic body radiation therapy (SBRT) in sequence with chemotherapy, but not surgery. Methods: In this retrospective study, we examined a cohort of 101 patients with stage II-III pancreatic cancer who underwent SBRT with sequential chemotherapy at a single institution (Stanford Health Care) between 1999-2020. From their pre-SBRT contrast-enhanced CT images with segmented tumors, delineating regions-of-interest, we extracted 900 radiomic (quantitative pixel-level imaging characteristic) features. In the first phase, we identified radiomic features that predicted rapid tumor progression within three months following SBRT. We divided the dataset into a training set (n = 53) for model development and a test set (n = 48) for evaluation. Using logistic regression with the Least Absolute Shrinkage and Selection Operator algorithm for feature selection and classification, we built a binary prediction model on the training set to identify patients at risk of progression within three months of SBRT. To fine-tune parameters, we performed five-fold cross-validation (CV) on the training set, repeating each set of parameters five times. We assessed model performance on the test set using the area under the curve (AUC). We selected the model with the best AUC, generating the predictive radiomic feature set. In the second phase, we conducted univariate and multivariate Cox regression analyses to assess the relationship between OS and individual clinical variables (age, sex, stage, vessel involvement, tumor location, performance status, body mass index, biological equivalent dose of radiation) and the radiomic feature set as high versus low risk. Results: Our cohort consisted of 48 men (mean age, 70 years ± 11 [SD]) and 53 women (mean age, 67 years ± 13 [SD]). From the first phase, 32 textural features comprised the radiomic feature set that best predicted rapid tumor progression, with mean AUCs of 0.852 (CV, n=53) and 0.814 (test, n=48). In the univariate Cox model, only the radiomic feature set was predictive of OS (hazard ratio, HR, 1.724, p=0.011). In the multivariate Cox model, radiomic features and age were significant predictors of OS, with HR of 1.819 (p=0.007) and 1.024 (p=0.024), respectively. Conclusions: CT-derived radiomic features predict rapid tumor progression following SBRT, confer nearly a twofold increase in mortality risk, and, along with patient age, enhance the identification of patients with stage II-III pancreatic cancer with poor OS. [Table: see text]
Prognostic impact of codon-specific KRAS mutational status on survival in patients with metastatic colorectal cancer treated with TAS-102 or regorafenib.
Authors: Hsieh Meng-Che , Rau Kun-Ming , Liu Kuang-Wen , Chiu Chong-Chi , Chen Chih-I , Song Ling-Chiao , Chen Hsin-Pao 
Published: August 2024

75 Background: Previous study demonstrated KRAS (Kirsten rat sarcoma virus) codon G12 mutation as a potential biomarker of resistance in metastatic colorectal cancer (mCRC). Our study aimed to evaluate the prognostic impact of codon-specific KRAS mutational status on survival in patients with mCRC treated with TAS-102 or regorafenib. Methods: mCRC Patients treated with TAS-102 or regorafenib were retrospectively enrolled into our study. Patients were classified into KRAS G12 (KRASG12) mutation and no KRASG12 mutation according to extended RAS testing. Survival was estimated for comparison, stratified by KRAS mutational status and treatment. Kaplan-Meier curves were estimated for overall survival (OS). Results: A total of 183 patients were enrolled into our study, with 91 patients treated with TAS-102 and 92 patients treated with regorafenib. The median age was 63 years old in our cohort. Most patients were male (54%) with left side colon (85%). After extended RAS/RAF mutational testing, 28% patients had KRASG12 mutation, 50% had RAS/RAFWT, 9% had KRASG13 mutation, 8% had KRASother mutation, 3% had NRAS mutation and 2% had BRAF mutation. For patients treated with TAS-102 group, 20% patients had KRASG12 mutation, while for regorafenib group, 38% patients had KRASG12 mutation. The median OS of TAS-102 was 4.5 versus 11.3 months for KRASG12 mutation and no KRASG12 mutation, respectively (p= 0.013). The median OS of regorafenib was 10.5 versus 6.3 months for KRASG12 mutation and no KRASG12 mutation, respectively (p= 0.183). Furthermore, 34% patients with KRASG12 mutation received TAS-102, while 56% patients without KRASG12 mutation received TAS-102. For patients with KRASG12 mutation, the median OS was 4.5 m versus 10.5 months for TAS-102 and regorafenib group, respectively (p= 0.113). For patients without KRASG12 mutation, the median OS was 11.3m versus 6.3 months for TAS-102 and regorafenib group, respectively (p= 0.047). Conclusions: The prognostic impact of KRASG12 was divergent between mCRC patients treated with TAS-102 and regorafenib. Codon-specific KRAS mutational status should be taken into consideration before treatment.
Research and analysis on the situation of diagnosis and treatment capabilities of breast cancer in China county.
Authors: Tan Xiang , Xin Yi , Yu Xiaohong , Zhang Huamao , Xu Youfu , Shen Biyu , Zhou Shunen , Liu Ling , Luo Fengmei , Kang Pengkun , Zhao Huarong , Zhang Zuowen 
Published: August 2024

8 Background: 1. In 2016, 306,000 breast cancer cases were newly diagnosed in China, with one-third in rural areas. Breast cancer ranked second in incidence (22.47/105) among female cancers in Sichuan Province. 2. Health resources are unequally distributed in China, especially in Sichuan Province where 43.27% reside rurally. County hospitals play a vital role in rural patients' diagnosis, treatment, and referrals. Methods: This cross-sectional observational study surveyed 124 county-level hospitals that had treated breast cancer in 183 counties in Sichuan Province from December 2023 to January 2024. Outcomes include: 1) hospital level; 2) oncology certification; 3) availability of dedicated breast department and staffing; 4) breast cancer diagnosis and treatment technology; 5) pre-treatment TNM staging rate; 6) anti-neoplastic drugs and support Accessibility of medicines. Results: Out of 124 hospitals surveyed, 6 excluded for zero breast cancer cases in 2023. The remaining 118 hospitals revealed: 1) 78.81% tertiary, 93.22% public; 2) 75.42% with special outpatient qualifications, 57.63% with concurrent special antineoplastic drug designations, 17.80% with one qualification; 3) 57.63% with dedicated breast units, but only 16.1% with specialized breast cancer staff; 4) 31.36% with full breast imaging modalities, 78.23% lacking mammography; PET-CT and bone scan availability: 5.93% and 9.32%; 5) 71.19% with independent pathology, but only 30.65% providing comprehensive services; 6) Surgeries for breast cancer: 86.44% (44.07% breast conservation), radiation therapy availability: 39.83%; 7) AJCC TNM staging rate: 77.12%; 8) Antineoplastic accessibility: conventional chemotherapy (93.22%), anti-HER2 therapy (28.81%), endocrine therapy (47.46%), CDK4/6 inhibitors (26.27%, with 41.53% having only one); 9) Analgesics: 87.90% (morphine 94.92%, tramadol 88.98%, fentanyl patches 34.75%, oxycodone 46.61%); antiemetics (5-HT3 antagonists 69.49%, NK1 antagonists 72.88%, olanzapine 48.31%, metoclopramide 64.41%); medications for hematologic toxicity: 51.61%. Conclusions: Shortages exist in specialized breast care units and trained personnel among county hospitals in Sichuan, China. Special outpatient qualifications and antineoplastic prescription credentials concentrated mainly at tertiary centers. Enhancing imaging and histopathology capacities for breast cancer diagnosis is an urgent need. While conventional chemotherapies demonstrate good accessibility, anti-HER2 targeted therapies, endocrine therapies, and CDK4/6 inhibitors covered by national insurance have limited availability. Enhanced provision of new antiemetics and analgesics is needed. [Table: see text]
Effect of statin use on long-term survival after diagnosis of colorectal cancer: Emulating hypothetical target trials using a nationwide real-world database.
Authors: Woo Hyeong-taek , Shin Aesun 
Published: August 2024

82 Background: Observational studies suggest that statin use after colorectal cancer (CRC) diagnosis is associated with improved survival. However, potential bias due to misalignment of time zero in observational studies may distort associations and therefore requires validation using robust epidemiological methods. We aimed to emulate a hypothetical randomized trial—a target trial—for estimating per-protocol effects of statin initiation in patients with incident colorectal cancer on long-term survival. Methods: To emulate a target trial using real-world data, we extracted information from 103,005 patients diagnosed with CRC between 2005 and 2015 from the Korean National Health Insurance (KNHI) database, encompassing health records for the entire Korean population. We excluded individuals who had been prescribed statins for at least 180 days before the CRC diagnosis or those with missing or incomplete demographic information. We set a 180-day grace period and compared the group that initiated statin treatment within 180 days after the CRC diagnosis with the non-statin group using the “clone-censor-weight” method. Patients' demographic and socioeconomic information, along with colorectal cancer treatment, were included as baseline covariates. Additionally, the Charlson Comorbidity Index (CCI) score was included both as a baseline covariate and as a time-varying covariate. Hazard ratios (HRs) for all-cause mortality and CRC-specific mortality within 60 months of baseline were calculated using pooled logistic regression models. Results: Among the 103,005 patients diagnosed with CRC, 88,516 were finally analyzed after the exclusion process. A total of 2,071 (2.3%) individuals initiated statin treatment during the grace period and 86,445 (97.7%) patients did not. Statin initiators, compared with statin noninitiators tended to be older (mean age: 65.7 vs. 62.6) and had a higher CCI score at baseline (mean CCI score: 1.38 vs.1.26). Individuals who initiated statin treatment did not reduce the hazard of all-cause mortality (The adjusted HR 1.01, 95% CI 0.98-1.04) and CRC-specific mortality (The adjusted HR 1.01, 95% CI 0.97-1.04). Conclusions: The results of the analysis after removing potential biases showed that statin was not related to improving survival in CRC patients. The study results conflict with those of previous observational studies but are consistent with the findings of other recently conducted target trial emulations.
First-line (1L) anti-PD-1 plus chemotherapy in HER2-negative advanced gastric cancer: Real-world evidence from a single Korean center.
Authors: Shim Joosung Gabriel , Jung Minkyu , Kim Hyunwook , Kim Kyoo Hyun , Kim Taeho , Kim Youhyun , Shim Hyo Sup , Kim Hyunki , Kim Hyo Song , Lee Choong-kun , Rha Sun Young 
Published: August 2024

83 Background: The implementation of immune checkpoint inhibitor combinations as first-line (1L) treatment has shown promising outcomes and is now the standard of care for HER2-negative advanced gastric cancer. However, real-world evidence supporting this approach as 1L treatment remains limited. Here, we present an analysis of real-world outcomes, comparing 1L anti-PD-1 combined with doublet chemotherapy to the previous standard chemotherapy. Methods: Patient from January 2005 to August 2023 were retrospectively reviewed. The study defined the molecular epidemiology cohort (M cohort) as patients with results for HER2, Epstein-Barr virus (EBV), mismatch repair (MMR), or PD-L1. HER2-negative patients who received palliative first-line chemotherapy doublet regimens with or without PD-1 inhibitor were included. Survival analysis included progression-free survival (PFS) and overall survival (OS), as well as subgroup analyses for molecular subtypes. Results: Total 3,028 were enrolled in the M cohort. The incidence rates of HER2-positive, EBV-positive, and deficient Mismatch Repair (dMMR) were 20.0% (606/3028), 3.8% (93/2432), and 4.7% (126/2660), respectively. PD-L1 testing was conducted on 1,394 patients, with 54.3% (1634/3028) having a CPS (Combined Positive Score) of ≥10, and 47.6% (664/1394) having a CPS of ≥1. Among these patients 1,527 had received chemotherapy doublet, and 153 had received chemotherapy doublet with PD-1 inhibitor as their 1L treatment. During a median follow-up of 56.5 months (95% CI,49.9-66.2), patients who had received PD-1 inhibitor combination therapy showed improved PFS (7.1 vs. 6.1 months; Hazard Ratio [HR], 0.77; 95% Confidence Interval [CI], 0.64–0.93) and OS (18.1 vs. 14.6 months; HR 0.80; 95% CI, 0.63–1.01) compared to those without it. The benefits in PFS from PD-1 inhibitor combination therapy were particularly notable in patients with deficient MMR status (HR, 0.22 vs. 0.80 in those without PD-1 inhibitor combination; p for interaction <0.05) and in patients with signet ring cell carcinoma histology (HR, 0.58 vs. 0.92 in those without PD-1 inhibitor combination; p for interaction <0.05). Conclusions: We observed real-world efficacy of the combination of PD-1 inhibitor and chemotherapy doublet as 1L treatment for HER2-negative advanced gastric cancer, consistent with previous clinical trials. [Table: see text]
Does liver cirrhosis affect outcomes in non-metastatic esophageal squamous cell carcinoma (ESCC) undergoing radiotherapy-based treatment?
Authors: Hua YuYang , Huang Shih Yu , Li Shau-Hsuan 
Published: August 2024

89 Background: Liver cirrhosis frequently coexists with esophageal squamous cell carcinoma (ESCC), as both conditions share alcohol consumption as a common etiological factor. Surgical intervention is often contraindicated or associated with significant morbidity in patients with non-metastatic ESCC and liver cirrhosis. Consequently, radiotherapy-based therapy is commonly employed. This study aims to investigate prognostic factors for overall survival in such patients undergoing radiotherapy-based therapy. Additionally, we will evaluate predictors for the 90-day mortality rate, proposed as a measure to mitigate treatment-related toxicity and prevent unwarranted or excessive medical interventions. Methods: From January 2001 to December 2021, we conducted a retrospective review of the medical records of 1298 patients diagnosed with esophageal squamous cell carcinoma (ESCC). Within this cohort, we identified 103 patients with concomitant liver cirrhosis, diagnosed through abdominal ultrasonography, computerized tomography, and/or liver biopsy, as appropriate. Of these individuals, 78 patients with non-metastatic ESCC and liver cirrhosis were included in our analysis. We collected clinicopathologic parameters and examined their correlation with overall survival and the 90-day mortality rate. Results: Univariate analysis revealed several factors significantly associated with inferior overall survival: Child-Pugh classification B/C (P<0.001, compared to A), radiotherapy alone (P=0.03, compared to chemoradiotherapy), prothrombin time prolonged by ≥2 seconds (P=0.024), albumin levels ≤3.5g/dl (P<0.001), controlled/refractory ascites (P=0.01, compared to no ascites), and total bilirubin levels ≥1.5mg/dl (P=0.004). In multivariate analyses, albumin levels ≤3.5g/dl (P=0.001, odds ratio: 2.500) and total bilirubin levels ≥1.5mg/dl (P=0.019, odds ratio: 2.012) were identified as independent prognostic factors. Among the 78 patients receiving radiotherapy-based therapy, the 90-day mortality rate was 10.3% (n=8). Clinical 8th AJCC stage IVA (P=0.02), clinical T classification T3/4 (P=0.049), prothrombin time prolonged by ≥4 seconds (P=0.009), and albumin levels ≤3.5g/dl (P=0.027) were significantly correlated with higher 90-day mortality rate. The logistic model indicated that albumin levels ≤3.5g/dl (P=0.015, odds ratio: 16.129) and clinical 8th AJCC stage IVA (P=0.012, odds ratio: 17.544) were independently associated with higher 90-day mortality rate. Conclusions: In patients undergoing radiotherapy-based therapy for non-metastatic esophageal squamous cell carcinoma (ESCC) and liver cirrhosis, pretreatment hypoalbuminemia has been associated with increased 90-day mortality and unfavorable prognosis.
Association of aberrant expression of CD39 with the outcome of patients with cholangiocarcinoma.
Authors: Zheng Bohao , Ni Xiaojian , Liu Houbao 
Published: August 2024

93 Background: Cholangiocarcinoma is defined as a kind of malignant tumor originating from bile ducts. Due to the lack of effective diagnostic and treatment methods, the prognosis of cholangiocarcinoma is dismal. Accumulating evidence indicates that CD39 could promote the progression of several types of cancer. However, the biological function and the underlying mechanism of CD39 in cholangiocarcinoma have not been well investigated. Methods: Quantitative reverse transcription PCR (RT-qPCR), western blot (WB), and immunohistochemistry staining was used to evaluate the expression level of CD39 in cholangiocarcinoma. Kaplan-Meier and Cox hazard ratio regression analyses were implicated to evaluate the prognostic significance of CD39. Cell counting kit-8 (CCK-8) was carried out to evaluate the proliferative capacity, while transwell assay was used to detect the migration and invasion ability. In addition, B-NDG mice were used for the in vivo assay. The potential protein binding with the CD39 was identified through co-immunoprecipitation. Results: We observed that CD39 was aberrantly expressed in the tumor tissue and cholangiocarcinoma cell lines. Our analysis indicated that the high expression level of CD39 correlated with aggressive clinicopathological characteristics, and CD39 was identified as an independent poor prognostic factor in cholangiocarcinoma. In addition, our in vitro and in vivo data indicated that the knockdown of CD39 could suppress the proliferation, migration, invasion ability, and the epithelial-mesenchymal transition (EMT) process of cholangiocarcinoma. Opposite results were observed when CD39 was overexpressed. Mechanistically, CD39 could bind with Annexin A2 (ANXA2), which influences the phosphorylation level of ANXA2 at the Tyr24 site, thereby promoting the activation of PI3K/AKT signaling, which resulted in the biological change in cholangiocarcinoma. Conclusions: Our data indicated that CD39 was overexpressed in the tumor tissue. Meanwhile, CD39 was identified as an independent prognostic factor of poor overall survival for patients withcholangiocarcinoma. In terms of the biological role of CD39, our data indicated that CD39 promoted the progression and metastasis of cholangiocarcinoma through binding with ANXA2, and through activating the PI3K/AKT signaling. In brief, CD39 is a potential prognostic factor and therapeutical target for cholangiocarcinoma.