bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of PD-L1 combined positive score (CPS) on clinical response to nivolumab in patients with advanced esophageal squamous cell carcinoma.
Authors: Matsubara Yuki , Toriyama Kazuhiro , Kadowaki Shigenori , Ogata Takatsugu , Nakazawa Taiko , Kato Kyoko , Nozawa Kazuki , Narita Yukiya , Honda Kazunori , Masuishi Toshiki , Bando Hideaki , Ando Masashi , Tajika Masahiro , Hosoda Waki , Muro Kei 
Published: June 2021

e16045 Background: The ATTRACTION-3 trial showed that nivolumab (Nivo) significantly improved overall survival (OS) of patients (pts) with previously treated advanced esophageal squamous cell carcinoma (ESCC) regardless of tumor programmed cell death ligand-1 (PD-L1) expression assessed with tumor proportion score (TPS). On the other hand, pembrolizumab prolonged OS in advanced esophageal carcinoma pts with combined positive score (CPS) of ≥ 10 in the KEYNOTE-181 trial. Whether CPS can predict clinical outcome of Nivo in advanced ESCC pts remains unclear. Methods: We retrospectively evaluated advanced ESCC pts who received Nivo at a single institution between January 2014 and September 2020. The main eligibility criteria were as follows: refractory or intolerant to fluoropyrimidines and platinum, no prior anti-PD-1/PD-L1 antibody treatment, no comorbid malignancies, and available tissue specimens obtained before initiation of Nivo. PD-L1 immunostaining was performed using PD-L1 IHC 22C3 pharmDx assay, and the tumors were classified into three groups depending on CPS (≥ 10, 1–10, < 1). The adjusted hazard ratios (aHRs) for progression-free survival (PFS) and OS were calculated using a multivariate Cox model that contained variables with p values < 0.05 in the univariate analysis. Results: Among 69 pts, 50 were eligible (CPS ≥ 10/CPS 1–10/CPS < 1, 23/18/9). Patient characteristics were as follows (CPS ≥ 10/CPS 1–10/CPS < 1): age, ≥ 65, 70/67/67%; male, 83/67/78%; PS ≥ 1, 61/72/44%; second-line treatment, 65/61/56%; disease status, recurrent, 61/33/78%; prior esophagectomy, 65/33/44%; prior radiotherapy, 57/56/56%; prior taxane, 52/28/44%; the number of metastatic sites, ≥ 2, 48/61/89%; lymph node metastasis, 78/83/89%, lung metastasis, 26/22/56%; liver metastasis, 17/17/44%. Among 42 pts (84%) with disease progression after Nivo treatment, 24 pts received salvage-line chemotherapy. The adjustment factor for PFS was liver metastasis, while that for OS was not detected. The median PFS was 4.1 months (mo) in CPS ≥ 10 and 2.5 mo in CPS 1–10 (HR vs. CPS ≥ 10, 1.06; 95% CI, 0.51–2.17; p = 0.864; aHR, 1.15; 95% CI, 0.54–2.36; p = 0.713), and 1.4 mo in CPS < 1 (HR vs. CPS ≥ 10, 3,78; 95% CI, 1.53–8.92; p = 0.005; aHR, 1.91; 95% CI, 0.67–5.39; p = 0.223). The median OS was 12.3 mo in CPS ≥ 10, 10.2 mo in CPS 1–10 (HR vs. CPS ≥ 10, 1.72; 95% CI, 0.75–4.00; p = 0.201), and 9.0 mo in CPS < 1 (HR vs. CPS ≥ 10, 2.31; 95% CI, 0.92–5.69; p = 0.075). Objective response rate (CPS ≥ 10/CPS 1–10/CPS < 1) in 40 pts who had measurable lesions were 32/25/0%, respectively. Conclusions: The pts with CPS of < 1 did not respond to Nivo. Our study suggests that CPS is useful for predicting response to Nivo in pts with advanced ESCC.[Table: see text]
A phase 1 multicenter, dose expansion study of ARX788 as monotherapy in patients with HER2-positive advanced gastric and gastroesophageal junction adenocarcinoma (ACE-Gastric-01).
Authors: Zhang Yang , Qiu Miaozhen , Wang Jufeng , Zhang Yanqiao , Yuan Xianglin , Zhang Tao , Yan Jinchun , Xiong Gaozhun , Ji Yanping , Liang Xuejun , Xia Gang , Xu Rui-hua 
Published: June 2021

e16059 Background: ARX788 is a novel antibody drug conjugate (ADC) that consists of human epidermal growth factor receptor 2 (HER2) targeted monoclonal antibody (mAb) linked to a cytotoxic payload, AS269, a highly potent tubulin inhibitor. In a phase 1 study of ARX788 in HER2-positive advanced breast cancer (CTR20171162/ACE-Breast-01), the objective response rate (ORR) was 74 % (14/19) at 1.5 mg/kg Q3W. Here we present the safety, tolerability, and antitumor activity of ARX788 in HER2-positive advanced gastric and gastroesophageal junction (GEJ) cancer in the phase 1 (ACE-Gastric-01) study. Methods: participants with HER2+ gastric/GEJ cancer were administrated with ARX788 intravenously at dose levels of 1.3, 1.5, and 1.7 mg/kg Q3W to determine the maximum tolerated dose and recommended phase 2 dose; and to evaluate the antitumor activity. Efficacy endpoints included objective response rate (ORR) and disease control rate (DCR) per RECIST v1.1. Results: As of Jan 29, 2021, a total of 23 participants including 9 at the 1.3 mg/kg and 14 at the 1.5 mg/kg received at least one dose of ARX788. All patients were heavily treated previously. The confirmed ORR was 42.9% and 46.2% at the 1.3 and 1.5 mg/kg, respectively. As of the cut-off date, six participants were still under treatment with two of them were treated for longer than 12 months. Most AEs were grade 1 or 2 and were manageable. There were 2 drug-related grade 3 AEs and no grade 4 or 5 AEs occurred. No DLT was observed and the MTD was not reached. The dose expansion at the 1.7 mg/kg Q3W cohort is still ongoing and the mature data will be presented later. Conclusions: ARX788 was well tolerated with promising antitumor activity in patients with HER2-positive advanced gastric and GEJ adenocarcinoma. Clinical trial information: CTR20190639. [Table: see text]
HERIZON: A phase 1B/2 open-label study of imu-131 HER2/neu peptide vaccine PLUS standard of care chemotherapy with randomization in phase 2 in patients with HER2/neu overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction.
Authors: Laeufle Rita , Maglakelidze Marina , Bulat Iurie , Ryspayeva Dinara , Zoran Andric , Chawla Tanuj , Nikolic Ivan , Nagarkar Rajnish , Venkata Giri , Choudhary Vaibhav , Radosavljevic Davorin , Singh Rajesh Kumar , Wiedermann Ursula , Good Anthony J , Ede Nick , Chong Leslie Mi Ok 
Published: June 2021

e16065 Background: The phase 2 part of the study hypothesizes HER-Vaxx (IMU-131) will provide treatment benefits consistent with traditional monoclonal antibodies that target HER2 in patients with confirmed Her2+ advanced or metastatic gastric cancer with a corresponding adaptive immune response without added toxicity. In the phase 1b dose finding part of the study tumor response of patients who received 50ug dose strongly correlated with antibody levels with 50ug selected as the phase 2 dose (Wiedermann et. al., 2019). Phase 2 is a randomized two arm study of either HER-Vaxx plus standard chemotherapy or standard chemotherapy alone. The primary endpoint is overall survival, with progression-free survival, safety and immune related changes in humoral and cellular immunogenicity secondary endpoints. Methods: Patients received SOC chemotherapy for a maximum of 6 cycles with the HER-Vaxx group also receiving 50ug dose of IMU-131 at Baseline/Day 0, Day 14, Day 35, Day 77 and then every 63 days until disease progression. The per protocol pre-planned first interim analysis (OS, PFS and safety) in a total of 27 patients after 15 progression events was reviewed by the independent data monitoring committee (IDMC). Results: Within ITT analysis, 8 of 27 patients died on the control arm and 4 on the HER-Vaxx plus SOC chemotherapy arm with an overall survival HR of 0.418 (2 sided 80% CI: 0.186, 0.942) and a 1-sided p-value of 0.083. Out of 27 patients, 9 patients progressed on the control arm while 6 patients progressed on the HER-Vaxx plus SOC chemotherapy arm with a HR of 0.532 (2 sided 80% CI: 0.267, 1.060) and a 1-sided p-value of 0.086. A robust HER2 specific antibody response developed in the HER-Vaxx arm compared to the control arm whereas there was no difference in safety between the two treatment arms. Conclusions: The IDMC confirmed that the safety of the study was favorable with no added toxicity of HER-Vaxx and SOC chemotherapy with a favorable risk-benefit for the combination. The study has completed enrollment and final data is expected in late 2021. Clinical trial information: NCT02795988.
Neoadjuvant programmed death-1 blockade plus chemotherapy in locally advanced esophageal squamous cell carcinoma.
Authors: Zhang Xu , Yang Guozhen , Su Xiaodong , Luo Guangyu , Cai Peiqiang , Zheng Yating , Bei Ting , Gao Chan , Huang Mengli 
Published: June 2021

e16076 Background: Immunotherapy is effective in treating advanced esophageal squamous cell carcinoma (ESCC), but little is known about its role in the setting of neoadjuvant therapy. Methods: Data from a retrospective cohort and a prospective cohort of locally advanced ESCC patients were analyzed. All patients included had received neoadjuvant camrelizumab plus nab-paclitaxel and S1 capsule followed by radical esophagectomy. The main purpose of this study was to evaluate the safety and feasibility of the neoadjuvant treatment. In addition, pathological response and the relationship between tumor immune microenvironment features (TIME)/tumor mutational burden (TMB) and treatment response were also explored. Results: A total of 25 locally advanced ESCC patients from both cohorts were included, of which 12 from the retrospective cohort and 13 from the prospective cohort. Only two patients experienced grade 3 or 4 adverse events, including onehad anemia and the other (4%) had limb numbness. No surgical delay or perioperative death was reported. Sixteen patients (64%) responded to the treatment, eight (32%) with a complete pathological response and eight (32%) with a major pathological response. Neither programmed death-ligand 1 expression nor TMB was correlated with treatment response. In terms of TIME analysis, patients with better pathological response in the primary tumor had significantly higher abundance of CD56dim natural killer cells (109 vs 32, P= 0.01), while lower density of M2-tumor-associated macrophages was associated with numerically better pathological response in the lymph nodes (47 vs 163.1, P= 0.55). Conclusions: Neoadjuvant camrelizumab plus nab-paclitaxel and S1 is safe, feasible and effective, and the efficacy could be predicted by TIME, which is worthy of further investigation. Clinical trial information: ChiCTR2000029807.
Improved lymph node metastasis prediction from preoperative esophageal squamous cell cancer CT by graph attention convolutional neural network (GACNN).
Authors: Ding Mingjun , Cui Hui , Li Butuo , Zou Bing , Xu Yiyue , Fan Bingjie , Li Wanlong , Yu Jinming , Wang Linlin 
Published: June 2021

e16093 Background: Lymph node (LN) metastasis is the most important factor for decision making in esophageal squamous cell carcinoma (ESCC). A more accurate prediction model for LN metastatic status in ESCC patients is needed. Methods: In this retrospective study, 397 ESCC patients who took Contrast-Enhanced CT (CECT) within 15 days before surgery between October 2013 and November 2018 were collected. There are 924 (798 negative and 126 positive) LNs with pathologically confirmed status after surgery. All LNs were randomly divided into a training set (n = 663) and validation set (n = 185). Data augmentation including shifting and rotation was performed in the training set, resulting in 1326 negative and 1140 positive LN samples. The GACNN model was trained over CT volumetric patches centred at manually segmented LN samples. GACNN was composed of a 3D UNet encoder to extract deep features, and a graph attention layer to integrate morphological features extracted from segmented LN. The model was validated using the validation set (135 negative and 50 positive) and measured by area under ROC curve (auc), sensitivity (sen), and specificity (spe). Results: GACNN achieved better auc, sen, and spe of 0.802, 0.765, and 0.826, when compared to 3 other models including CT radiomics model (auc 0.733, sen 0.689, spe 0.765), 3D UNet encoder (auc 0.778, sen 0.722, spe 0.767), and our model without morphological features (auc 0.796, sen 0.754, spe 0.803). The improvement was statistically significant (p < 0.001). Conclusions: Our prediction model improved the prediction of LN metastasis, which has the potential to assist LN metastasis risk evaluation and personalized treatment planning in ESCC patients for surgery or radiotherapy.
Correlation of patient characteristics with clinical outcomes of camrelizumab combined with apatinib for unresectable hepatocellular carcinma (uHCC): An observational retrospective analysis.
Authors: Liu Gang , Gong Liansheng , Zhou Wenxuan , Li Xiaoli , Wang Fei , He Tingting , Zhao Juan 
Published: June 2021

e16120 Background: There is limited data on clinical parameters to evaluate the therapeutic effects on immune checkpoint inhibitors (ICIs) combined with anti-angiogenic agent for uHCC. Here, we assessed efficacy and safety of camrelizumab combined with apatinib for uHCC from real-world data, and performed the retrospective subgroup analysis to investigate the potential factors related to therapy response and patients survival as well. Methods: We evaluated clinical data and outcome of 26 uHCC patients who received camrelizumab 200 mg intravenously every 2 weeks combined with apatinib 250 mg qd between May 2019 and Jul 2020. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) were evaluated using independent central review mRECIST and RECIST 1.1. Treatment related adverse events (TRAEs) and immune-related adverse events (irAEs) were evaluated. Results: The patients’ characteristics of our cohort are summarized in Table. Overall, our study shows that ORR was 57.7% (mRECIST), DCR was 84.62% (mRECIST), median PFS (mPFS) and OS (mOS) were 11 months and 18.2 months, respectively. For subgroup analysis, patients with first-line therapy (n=22) had dramatically better mPFS than non-first-line (15.0 vs. 4 months; p=0.01). Patients with baseline serum alpha-foetoprotein (AFP) > 400 ng/ml shows better therapeutic efficacy ( p<0.001). The patients with decreased AFP level after treatment had significantly longer mPFS (15.0 vs. 4 months; p<0.001) and mOS (NR vs. 5.7 months; p<0.001) than others. Overall, 14 (53.85%) patients had grade≥3 TRAEs, only 3 (11.54%) patients had grade≥2 irAEs. Conclusions: The first up-to-date real-world evidence indicates that both the baseline and post-treatment AFP level might be independent prognostic factors to evaluate the therapeutic efficacy and clinical outcome on the combination therapy of camrelizumab and apatinib. While larger sample sizes and longer follow-up study are needed to verify reliability of statistical results.[Table: see text]
Landmark analysis of overall survival (OS) by objective response (OR) in previously treated patients (pts) with advanced hepatocellular carcinoma (aHCC): Post hoc analysis of the randomized, phase 3 KEYNOTE-240 study.
Authors: Zhu Andrew X. , Cattan Stéphane , Merle Philippe , Daniele Bruno , Chan Stephen Lam , Yau Thomas , Bouattour Mohamed , Lim Ho Yeong , Chao Yee , Knox Jennifer J. , Ogasawara Sadahisa , Garrido Marcelo , Cheng Ann-Lii , Edeline Julien , Finn Richard S. , Siegel Abby B. , Rahman Ahmadur , Liu Chih-Chin , Kudo Masatoshi 
Published: June 2021

e16122 Background: Studies have shown that OR is prognostic of OS in pts with HCC. KEYNOTE-224 (NCT02702414) evaluated pembrolizumab (pembro; anti–PD-1) in sorafenib (sora)-treated pts with aHCC and showed an ORR of 17% that was durable in responders receiving pembro, ultimately leading to FDA approval. In KEYNOTE-224, a landmark analysis showed that OR in pembro-treated pts was prognostic of longer OS. The KEYNOTE-240 (NCT02702401) study evaluated pembro + best supportive care (BSC) vs placebo (pbo) + BSC in sora-treated pts with aHCC. Although clinical benefit was observed in KEYNOTE-240 with pembro vs pbo, prespecified statistical significance criteria for OS and PFS were not met. This post hoc analysis of KEYNOTE-240 was performed to determine whether OR at landmark is prognostic of longer survival after landmark time. Methods: Eligible pts were aged ≥18 y, had confirmed aHCC, and experienced progression during or after sora treatment or intolerance to sora. Landmark analyses of OS according to OR at 6, 12, and 18 wk after randomization were performed on the pembro arm to evaluate the association between survival after the landmark with response achieved before the landmark. OR was assessed by blinded independent central review per RECIST v1.1. Responders at each landmark were defined as pts with any response assessment of CR or PR before the landmark date; all other pts were defined as nonresponders. HR and 95% CI for survival after the landmark were calculated from the Cox proportional hazards model using Efron method of tie handling, with responder status as a single covariate. Analysis was performed on the ITT population. Results: As of Jan 2, 2019, median time from randomization to data cutoff was 21.2 mo (range 13.4-30.4) for pembro. In the pembro arm, 51 pts (18.3%) had a best OR of CR or PR and 6 pts (4.4%) in the pbo arm had a best OR of PR (no CR) (excluded from landmark analyses). OS after landmark time was longer for responders than nonresponders at the wk 6, 12, and 18 time points (Table). The HR for OS after landmark time for responders vs nonresponders was 0.37 (95% CI 0.18-0.75), 0.39 (95% CI 0.23-0.66), and 0.37 (95% CI 0.21-0.63) at wk 6, 12, and 18, respectively. Conclusions: This post hoc analysis showed that pts with sora-treated aHCC who achieved OR by landmark time with pembro have longer OS after the landmark time, confirming the prognostic association between OR with pembro and OS observed in KEYNOTE-224. Clinical trial information: NCT02702401. [Table: see text]
Trends in primary gallbladder cancer incidence and incidence-based mortality in the United States, 1973 to 2015.
Authors: Low Soon Khai , Giannis Dimitrios , Dinh Thuong Nguyen , Nam Nguyen Hai , Alshareef Abdulmueti , Moris Dimitrios , Lee Shin Yin , Ammad Ud Din Mohammad , Huy Nguyen Tien 
Published: June 2021

e16133 Background: Primary gallbladder carcinoma (GBC) is the most common biliary tract cancer with poor survival despite aggressive treatment. The purpose of our study was to investigate the trends of GBC incidence and incidence-based mortality (IBM), as well as to identify the factors responsible for any observed changes. Methods: GBC cases diagnosed between 1973 and 2015 were retrieved from the Surveillance, Epidemiology, and End Results database (SEER) database. Incidence and IBM rates age-adjusted to the 2000 US standard population were calculated and were stratified according to population and tumor-associated characteristics. Joinpoint Regression Analysis program was used to calculate the annual percent changes (APCs) for trend analysis. Results: Among the 10,792 patients with GBC, there was a predominance of white (81%) and female (71%) patients. The overall incidence rate was 1.086 (95% CI: 1.065 to 1.106) and the overall IBM rate was 0.995 (95% CI: 0.976 to 1.015). GBC incidence decreased by 1.645% (95% CI: 1.448 to 1.842, p < 0.001) per year, but the decreasing trend was only statistically significant from 1973 to 2002, after which the incidence rates stabilized. Conversely, IBM decreased by 1.689% (95% CI: 1.217 to 2.159, p < 0.001) per year from 1980 to 2015; the degree of decline in IBM rates during 1997-2015 (-1.194, 95% CI: -1.680 to -0.705, p < 0.001) was lower compared to that during 1980-1997 (-3.132, 95% CI: -3.682 to -2.578, p < 0.001). Mortality rates of GBC decreased in all age groups and in all races except for African American. There was a significant decrease in IBM in all SEER stages of GBC, except for distant stage GBC. Conclusions: GBC incidence and IBM rates have been decreasing over the last 40 years. However, the decrease in incidence and IBM appeared to have plateaued in the last two decades. The roles of increasing widespread use of laparoscopic cholecystectomy and use of newer treatment modalities, such as adjuvant chemotherapy and radiation, need to be investigated further.[Table: see text]
The PATH score based on pathological grade predicts survival of patients with advanced hepatocellular carcinoma after hepatic arterial infusion chemotherapy.
Authors: Lai Jinfa , Lyu Ning , Zhao Ming 
Published: June 2021

e16134 Background: Hepatic arterial infusion chemotherapy (HAIC) is an emerging and effective therapeutic strategy for advanced hepatocellular carcinoma (HCC). We developed a practical prognostic score for patients undergoing HAIC to determine who can benefit from it. Methods: Between 2014 and 2019, 482 treatment-naïve patients with advanced HCC undergoing HAIC were included from two independent treatment departments. Patients were randomly divided into training (n = 337) and validation (n = 145) cohorts. Pathological grade, ALBI grade, and TNM stage were selected and developed a simple score to evaluate HAIC treatment (PATH) by Cox regression model, subsequently confirmed in the validation cohort and compared with other prognostic scores. Results: According to the PATH score, patients were divided into three groups; low-risk (0-1 point), moderate-risk (2-3 points), and high-risk (4-6 points). The median survival in the low-risk group was significantly longer than those in the other two groups (34.9 [95% CI: 25.8-44.0] vs. 13.6 [95% CI: 11.3-15.9] vs. 8.0 [95% CI: 6.8-9.2] months; p <0.001). The PATH score was fairly confirmed in the validation cohort and consistently performed better than other existing models in the training and validation cohorts. Conclusions: PATH score may be a simple and practical tool, which has good discrimination ability to screen HAIC sensitive populations and effectively predict individual survival outcomes. Calculation method of the PATH score.[Table: see text]