bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Arabic version of swallowing quality of life questionnaire
Authors: Abdou Rania Mohamed , Elsayed Heba Elsayed , Adel Sally Mohamed 
Published: January 2021

Abstract
Background
Dysphagia is caused by sensorimotor function disruption of swallowing. In 2000, McHorney et al. first developed the SWAL-QOL (swallowing quality of life questionnaire). It is considered to be one of the initial self-rated tools which is dysphagia-specific.
The SWAL-QOL has been translated into many languages such as Dutch, French, Chinese, Swedish, Persian, German, and Arabic (its linguistic validation was tested only but its validation and reliability has not been determined). The aim of this study was to determine the validity and reliability of the Arabic version of SWAL-QOL (ASWAL-QOL) in adult patients complaining of oropharyngeal dysphagia. Patients were enrolled from the outpatient swallowing clinic of Main University hospitals starting from the first of March 2018 to the end of May 2019. According to these criteria, sums of 100 patients were involved in the study and they completed the ASWAL-QOL together with Dysphagia Handicap Index (DHI).

Results
There was a strong correlation between the eating desire, eating duration, and food selection in ASWAL-QOL and the functional domain in (DHI). This was found as well between mental health and social functioning in ASWAL-QOL and emotional domain in (DHI) that was used for convergent validity. While checking reliability, nearly most of the domains demonstrated stability over short term as well as excellent internal consistency reliability.

Conclusion
The current study illustrated that the ASWAL-QOL questionnaire is a valid and reliable tool to evaluate the impact of difficulties in swallowing on the quality of life in patients suffering from oropharyngeal dysphagia.
Single nucleotide polymorphisms (SNPs) in endoplasmic reticulum (ER) stress response genes to predict first-line treatment outcome in patients (pts) with metastatic colorectal cancer (mCRC): Data from the MAVERICC and FIRE-3 trials.
Authors: Battaglin Francesca , Arai Hiroyuki , Millstein Joshua , Stintzing Sebastian , Parikh Aparna Raj , Wang Jingyuan , Kawanishi Natsuko , Soni Shivani , Wu Zhang , Mancao Christoph , Heinemann Volker , Lenz Heinz-Josef 
Published: January 2021

103 Background: ER stress, triggered by the disruption of intracellular protein homeostasis, promotes the activation of a highly conserved adaptive program called unfolded protein response (UPR). UPR signaling has been reported to contribute to tumor initiation and progression, as well as microenvironment remodeling and chemoresistance in multiple cancer types, including CRC. Several studies point to a direct role of the UPR in tumor angiogenesis and an interaction with EGFR signaling. We therefore hypothesized that genetic variants in ER stress response genes may predict first-line treatment outcome in mCRC pts. Methods: The impact on outcome of 17 functional SNPs in 8 core genes of the ER stress response pathway ( IRE1, PERK, ATF6, XBP1, CHOP, GRP78, GADD34, ATF4) was analyzed on a total of 560 pts enrolled in two independent randomized first-line trials: MAVERICC (FOLFIRI/bevacizumab, [bev] n = 163; FOLFOX6/bev, n = 161), and FIRE-3 (FOLFIRI/bev, n = 107; FOLFIRI/cetuximab [cet], n = 129). Genomic DNA from blood samples of pts was genotyped through the OncoArray, a custom array manufactured by Illumina. The association between SNPs and clinical outcomes was evaluated using Cox regression and log-rank tests. The SNP*treatment interaction was assessed in both trials. Results: IRE1 rs16947383 any T allele variant was associated with shorter progression free survival (PFS) and overall survival (OS) compared to the C/C genotype in pts treated with FOLFIRI/bev in the MAVERICC trial both in uni- and multivariate analysis: 10.5 vs 14.1 months for PFS, adjusted hazard ratio (HR) 1.83, 95% confidence interval (CI) 1.12-2.99, adjusted P-value = 0.02; 23.8 vs 38.4 months for OS, adjusted HR 2.12, 95%CI 1.1-4.09, adjusted P-value = 0.02. The association with OS was validated in the FIRE-3 FOLFIRI/bev arm where any T allele carriers showed significantly shorter OS compared to the C/C genotype in both uni- and multivariate analysis: 21.1 vs 44.2 months, adjusted HR 2.06, 95%CI 1.01-4.18, adjusted P-value = 0.05. This effect was not observed in MAVERICC FOLFOX6 and FIRE-3 cet cohorts. A significant interaction was found between IRE1 rs16947383 and treatment on OS in both trials: P = 0.04 in MAVERICC (FOLFIRI vs FOLFOX6), and P = 0.03 in FIRE-3 (bev vs cet). In the MAVERICC FOLFOX6/bev arm, XBP1 rs2239815 and PERK rs6731022 SNPs were associated with shorter PFS and OS, while GADD34 rs610308 with longer OS, in multivariable analysis ( P < 0.05). Conclusions: Our results provide evidence that germline polymorphisms in ER stress response genes may have a predictive value in mCRC pts receiving first-line bev-based treatment and contribute to modulate anti-VEGF efficacy.
Racial differences in tumor biology and treatment of gastric cancer in the United States.
Authors: Tseng Joshua , Miller James , Feng Xiaoxi , Gangi Alexandra , Gong Jun , Burch Miguel 
Published: January 2021

174 Background: Racial disparities for gastric cancer are often identified in the literature. Although patients in Asia consistently demonstrate a survival benefit compared to those in the West, Asian patients in the US still retain this advantage, which suggests that tumor biology may be a major factor. The goal of our study is to identify racial differences in patient demographics, tumor biology and treatment for gastric cancer in the United States. Methods: The National Cancer Database was queried from 2006-2016 for patients with a diagnosis of gastric adenocarcinoma. Patient demographics, tumor characteristics, and treatment patterns were compared by patient ethnicity (White, Black, Hispanic, and Asian) with Kruskal-Wallis test and Pearson’s chi-squared test. Kaplan-Meier survival curves used to assess overall survival, and cox regression used to identify independent prognostic factors for survival. Results: 116,717 patients with gastric cancer identified; 78,066 were White, 17,486 were Black, 8,494 were Asian, and 12,671 were Hispanic. White patients were most likely to be older than 70 and have proximal tumors, and least likely to have diffuse type adenocarcinoma. Hispanic and Black patients were most likely to present with metastases. Asian patients were most likely to receive surgery and least likely to receive chemotherapy or radiotherapy. Stage for stage, Asians had the longest median survival, followed by Hispanic, Black, and White patients. Prognostic factors associated with a survival benefit include Asian ethnicity (HR 0.72, 95% CI 0.68-0.74), Hispanic ethnicity (HR 0.76, 95% CI 0.73-0.79), Black ethnicity (HR 0.95, 95% CI 0.93-0.98), private insurance (HR 0.91, 95% CI 0.87-0.96), higher income (HR 0.85, 95% CI 0.82-0.88), treatment at academic center (HR 0.87, 95% CI 0.83-0.91), higher-volume centers (HR 0.90, 95% CI 0.87-0.93), receiving surgery (HR 0.42, 95% CI 0.41-0.43), chemotherapy (HR 0.56, 95% CI 0.55-0.57), and radiation (HR 0.96, 95% CI 0.93-0.98). Conclusions: Treatment differences between Eastern and Western countries for gastric cancer persist between ethnic groups within the United States, with Asian patients retaining a survival benefit. Black and Hispanic patients present with aggressive disease and unfavorable socioeconomic factors that are detrimental to overall survival.
A phase I study to evaluate the safety of multiantigen stimulated tumor specific cell therapy (MASCT-I) in subjects with advanced gastric cancer.
Authors: Bu Zhaode , Jia Ziyu , Ji Ke , Ji Xin , Zhang Ji , Wu Xiaojiang , Kong Yanjun , Zhu Aimin , Li Xiaoshuang , Ji Jiafu 
Published: January 2021

200 Background: Gastric cancer was the fifth cancer world wide and the third leading cause of cancer-related death. PD-1 antibody has been approved for treatment in gastric cancer patients with positive expression of PD-L1 and microsatellite instability. MASCT-I (Multi-Antigen Stimulated Cell Therapy-I Injection) is an autologous non-engineered immune cell therapy for solid tumor, it is composed of multiple-antigen peptides(15 tumor associated antigens) loaded mature dendritic cells (DCs) and in vitro DC stimulated and proliferated effector T cells, the combination of MASCT-I and PD1 antibody could have a synergistic anti-tumor effect. Methods: This is a single center, phase I trial to explore the safety and tolerance of the combination of MASCT-I and PD-1 antibody in advanced gastric cancer (NCT03393416). 15 patients with PD-L1 expression or microsatellite instability were enrolled between April 2018, and June 2019. Camrelizumab was administered once every two weeks, DC and T cells were sequential administered once a month. Therapy continued until the disease progresses. Results: Only adverse reaction below grade 2 was observed related to MASCT-I,such as fever, fatigue etc. Abnormal liver function and reactive capillary hyperplasia may be related to Camrelizumab. Among the 15 patients, the longest treatment duration was 18.9 months, and the median progression-free survival (mPFS) was 3.93 months, among which, mPFS of patients with microsatellite instability is 10.23 months, mPFS of patients expressing PD-L1 is 2.35 months, which is slightly higher than the historical data of Camrelizumab alone in the treatment of advanced gastric cancer (8 weeks for mPFS). The patient 1002 always had high content of CD8+ cells and NK cells and the positive immune response in their bodies, which may plays a role in killing the tumor cells. Conclusions: The combination of MASCT-I and Camrelizumab in the treatment of advanced gastric cancer or gastroesophageal junction cancer is a safe treatment regimen, and its efficacy deserves further study. Clinical trial information: NCT03393416.
Three-year follow-up of ATTRACTION-3: A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy.
Authors: Chin Keisho , Kato Ken , Cho Byoung Chul , Takahashi Masanobu , Okada Morihito , Lin Chen-Yuan , Kadowaki Shigenori , Ahn Myung-Ju , Hamamoto Yasuo , Doki Yuichiro , Yen Chueh-Chuan , Kubota Yutaro , Kim Sung-Bae , Hsu Chih-Hung , Holtved Eva , Xynos Ioannis , Matsumura Yasuhiro , Takazawa Akira , Kitagawa Yuko 
Published: January 2021

204 Background: Previous results from the ATTRACTION-3 phase 3 trial demonstrated a significant improvement in overall survival and a favorable safety profile compared with taxane chemotherapy (CT) in previously-treated ESCC patients. To our knowledge, no long-term efficacy and safety data of this immune checkpoint inhibitor has been reported in ESCC. Herein, we report the three-year survival data of Nivo in ESCC. Methods: In ATTRACTION-3, 419 patients with unresectable advanced or recurrent ESCC refractory or intolerant to 1 prior fluoropyrimidine/platinum-based CT were randomized in a 1:1 ratio to receive Nivo (N = 210) or the investigator’s choice of CT (paclitaxel or docetaxel) (N = 209) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). A subgroup analysis of OS according to the best overall response (BOR) was performed. The onset of treatment-related adverse events of special interest over time in the Nivo arm was also evaluated. Results: As of data cut-off on 25 May 2020, 3 years after the last patient was enrolled, the median OS (mOS) was 10.91 months with Nivo versus 8.51 months with CT [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.64-0.97]. The OS rates of patients with Nivo and CT were 20.2 % and 13.5 % at 24 months, and 15.3% and 8.7% at 36 months, respectively. In the subgroup analysis of OS by BOR, mOS in CR/PR patients were 19.91 and 15.41 months (HR 0.84, 95%CI 0.46-1.54) and that in SD patients were 17.38 and 9.36 months (HR 0.45, 95%CI 0.26-0.78) in the Nivo and CT arm, respectively. Furthermore, mOS in PD patients were 10.91 and 6.18 months (HR 0.56, 95%CI 0.33-0.95) in the Nivo and CT arm, respectively. No new safety signals were detected during the three-year follow-up. Time to onset of the event of special interest was within the range of events previously observed in other indications. Conclusions: At three-year follow up, Nivo continued to show improved OS over CT in pretreated patients with advanced ESCC patients. Nivo showed a longer mOS than CT regardless of BOR. During the three-year follow-up, no new safety signals were observed. Clinical trial information: NCT02569242.
Phase I study of BI 754091 plus BI 754111 in Asian patients with gastric/gastroesophageal junction or esophageal cancer.
Authors: Yamaguchi Kensei , Kang Yoon-Koo , Oh Do-Youn , Kondo Shunsuke , Rha Sun Young , Kuboki Yasutoshi , Morimoto Manabu , Hara Hiroki , Lin Chia-Chi , Tachibana Yoshifumi , Hou Jianrui , Elgadi Mabrouk M. , Kitano Shigehisa 
Published: January 2021

212 Background: Dual blockade of immune checkpoint molecules, PD-1 and LAG-3, has been proposed to restore T-cell function and thus enhance antitumor responses. This Phase I trial evaluated BI 754091 (anti-PD-1) with BI 754111 (anti-LAG-3) antibodies in Asian pts with advanced solid tumors (NCT03433898). Here, we present results from pts with anti-PD-(L)1 inhibitor-naïve gastric/gastroesophageal junction or esophageal cancer (Cohorts A and B). Methods: In Parts 1 and 2 (dose escalation), the recommended dose for the combination was determined as BI 754091 240 mg + BI 754111 600 mg IV Q3W. In Part 3, the combination was assessed in expansion cohorts including pts with gastric/gastroesophageal junction cancer (Cohort A) and esophageal cancer (Cohort B). Eligible pts had received ≥1 line of prior systemic therapy but no prior anti-PD-(L)1 therapy. The primary endpoint in Part 3 was objective response (OR; confirmed complete response or partial response [PR]) per RECIST 1.1. Results: In Cohort A/B, 36/37 pts were treated:26/31 (72/84%) male, median age 60/63 years. Patients were enrolled in Taiwan (1/7 pts, 3/19%), Japan (12/27 pts, 33/73%) or Korea (23/3 pts, 64/8%). The median number of regimens of prior systemic therapy was 2/2 (Cohorts A/B, range: 16/14). All pts in Cohort B had squamous cell carcinoma. At the time of analysis, pts in Cohort A/B had undergone a median of 84/73 days on treatment (range: 31346/8325), from the start of treatment until the date of snapshot, death or discontinuation. Confirmed OR (PR) was observed in 4/7 pts in Cohorts A/B; overall response rate (ORR) was 11% and 19%. Stable disease (SD) was observed in 10/8 (28/22%) pts in Cohorts A/B and overall disease control rate was 39/41%. In Cohorts A/B, adverse events (AEs) and treatment-related AEs were experienced by 30/34 (83/92%) and 12/22 (33/59%) pts, respectively. The most commonly reported AEs were pyrexia (25/19%), decreased appetite (17/19%), increased aspartate aminotransferase (11/14%), anemia (11/11%) and nausea (6/14%). In Cohort A/B, 9/15 (25/41%) pts experienced immune-related AEs, most commonly rash in Cohort A (4 pts; 11%) and hyperthyroidism in Cohort B (4 pts; 11%). In Cohorts A/B, 2/6 (6/16%) patients experienced AEs leading to discontinuation of treatment. Conclusions: Treatment was well tolerated and preliminary antitumor activity was seen. Addition of LAG3 did not improve ORR beyond that expected for an anti-PD-1 monotherapy in gastric and esophageal cancer without patient selection. Clinical trial information: NCT03433898. [Table: see text]
A multi-institutional phase Ib/II trial of first-line triplet regimen (Pembrolizumab, Trastuzumab, Chemotherapy) for HER2-positive advanced gastric and gastroesophageal junction cancer (PANTHERA Trial): Molecular profiling and clinical update.
Authors: Rha Sun Young , Lee Choong-kun , Kim Hyo Song , Kang Beodeul , Jung Minkyu , Kwon Woo Sun , Bae Woo Kyun , Koo Dong-Hoe , Shin Su-Jin , Jeung Hei-Cheul , Zang Dae Young , Chung Hyun Cheol 
Published: January 2021

218 Background: We report the updated clinical data and molecular profiling results of a multi-institutional phase Ib/II trial of triple combination (pembrolizumab, trastuzumab, and chempotherapy) as first line therapy for HER2 positive advanced gastric and gastroesophageal junction (AGC/GEJ) cancer. (PANTHERA trial; NCT02901301). Methods: Pembrolizumab 200mg IV D1, Trastuzumab 6mg/kg (after 8mg/kg load) D1, Capecitabine 1000mg/m2 bid D1-14, and Cisplatin 80mg/m2 D1 every 3 weeks was selected as recommended phase II dose. The primary endpoint for phase II was ORR per RECIST v1.1. Secondary endpoints included PFS, OS, DOR, safety, and predictive biomarker analysis by targeted NGS. Results: At the time of data lock on Aug 31, 2020, total of 43 patients were treated with median follow up of 18.2 months, and 3 patients remained on the treatment, and 6 patients finished 2-year treatment without progression. ORR was 76.7% (CR 16.3%, PR 60.5%, conversion surgery 4.6%) with 26 pts (56.6%) showing more than 50% of tumor burden reduction. Median PFS was 8.6 months (95% CI 7.2-16.5) and median OS was 19.3 months (95% CI 16.5-NR). There were no MSI-H/dMMR or EBV-positive pts. No patient discontinued pembrolizumab because of immune-related adverse events. Clinical features including PD-L1 status (55.3% of pts ≥ CPS 1 and 13.2% of pts ≥ CPS 10 among available 38 pts), metastatic organ or baseline tumor burden was not related to the survival. Ninety-eight tumor tissues from 39 pts (paired tumor tissues from 22 pts) were analyzed with targeted NGS. Although every pts were HER2 IHC-positive, baseline HER2 amplification by NGS was related to the survival ( HER2 amp (n=8) vs HER2 non-amp (n=23); mPFS, not reached vs 7.7 months, P=0.0178; mOS, not reached vs 17.9 months, P=0.044) but no other signaling pathways predicted pts’ survival. HER2 mutations including L869R or D769H were related to the acquired resistance. High TMB showed a tendency toward better survival (mPFS; High (n=7) vs Low (n=24) TMB, 22.0 vs 8.2, P=0.2835) due to small number of patients. Updated immune markers and serial NGS analyses will be presented. Conclusions: First-line triplet regimen (Pembrolizumab, Trastuzumab, and Chemotherapy) showed promising efficacy based on HER2 amplification by NGS regardless of PD-L1 status in AGC/GEJ cancer. Correlative biomarkers found from NGS study need to be validated through on-going phase III Keynote-811 study. Clinical trial information: NCT02901301. [Table: see text]
The immune checkpoint CD73 (NT5E) in gastric adenocarcinoma (GAC): Biological characterization and clinical implications.
Authors: Salati Massimiliano , Spallanzani Andrea , Gelsomino Fabio , Botticelli Andrea , Cerbelli Bruna , Riggi Laura , Bocconi Alessandro , D'Onofrio Raffaella , Benatti Stefania , Luppi Gabriele , Dominici Massimo 
Published: January 2021

235 Background: CD73, an ecto-5’-nucleotidase (NT5E), serves as an immune checkpoint by generating adenosine, which in turn leads to immune-suppression and immune-escape. Elevated tissue levels of CD73 have been linked to poor patient survival across several cancer types and CD73 blockade is currently being tested in clinical trials. The biological role of CD73 and its translational relevance is largely unexplored in gastric adenocarcinoma (GAC). Methods: Data mining from transcriptomics big data sources including GEPIA2, HPA and Coexpedia platforms was performed to extract relevant information regarding CD73 expression profile, co-expressed network, association with clinico-pathologic features and survival of GAC. Difference between groups were evaluated by Student's t-test, while correlation analysis was performed through Pearson’s coefficient. Kaplan-Meier methods was used to estimate survival and log-rank test to make comparison between curves. Results: RNA sequencing expression data of 9,736 tumors and 8,587 normal tissue samples from the TCGA and the GTEx projects were analyzed. CD73 mRNA was significantly more expressed in tumour (n = 408) compared to paired normal samples (n = 211) (16.19 vs 3.5 transcripts/million; p < 0.001) and its expression level increased with pathologic stage (from stage I to III). CD73 gene was listed among the top-ten survival-associated genes (p = 4.74e-5) in GAC and together with FGF1 it displayed the greatest survival contribution in this disease among clinically validated genes. Regarding its impact on survival, GAC patients with high CD73 expression (n = 192) experienced a poorer overall survival (OS) compared to the low CD73 group (n = 192) (HR 1.9; log-rank p < 0.001), while regarding relapse-free survival (RFS), the unfavourable value of CD73 expression emerged after 20 months (HR 1.3; log-rank p = 0.23). The prognostic role on OS was validated in a cohort of 354 GAC, where high CD73 expression resulted in 5-year OS of 19% vs 46% (p = 0.00010). When inquiring for context-associated co-expression networks, Caveolin 1 (score = 10.939), FOS-like antigen 1 (score = 7.525) and plasminogen activator urokinase receptor (score = 7.422) were top-ranked co-expressed genes. Conclusions: In this hypothesis-generating analysis, we provided insights into CD73 expression pattern, co-expression networking and prognostic significance in GAC. Future studies in clinically annotated populations are warranted to confirm the value of CD73 in GAC.
Association of B cells in tumor microenvironment (TME) with clinical benefit to programmed cell death protein-1 (PD-1) blockade therapy in esophageal squamous cell carcinoma (ESCC).
Authors: Guo Jhe-Cyuan , Hsu Chia-Lang , Huang Yen-Lin , Lin Chia-Chi , Huang Ta-Chen , Chang Chun-Jung , Kuo Hung-Yang , Hsu Chih-Hung 
Published: January 2021

237 Background: Previous studies have indicated B cells as potential predictive markers for anti-PD-1 blockade therapy in several cancer types. The study explored whether B cells in TME and B cell related gene signatures are associated with clinical benefit (CB) for ESCC patients receiving anti-PD-1/PD-ligand 1 (PD-L1) therapy. Methods: Sixty-six ESCC patients treated with PD-1/PD-L1 blockade-based immunotherapy were enrolled. Tumor response was evaluated per RECIST 1.1, and CB was defined as complete response, partial response or stable disease at least 6 months. Transcriptome of formalin-fixed paraffin-embedded ESCC tissues were generated by NanoString nCounter platform with Human PanCancer Immune Profiling panel (n=25), Gene Set Enrichment Analysis (GSEA) was performed to identify the differential immune-related pathways, and CIBERSORT was applied to estimate the levels of infiltrating immune cells. The expression of CD20 was evaluated by immunohistochemistry (IHC) (n=66). Results: Of 66 enrolled patients (M: F= 65: 1, median age of 59), 44 and 22 were of recurrent and de novo metastatic ESCC. Forty and 26 received PD-1/PD-L1 blockade alone and PD-1/PD-L1-based combination immunotherapy, respectively. The response rate was 17%, and the CB rate was 24%. The median progression-free-survival (PFS) and overall survival are 1.8 and 5.5 months, respectively. B cell signature was significantly increased in patients with CB ( P < 0.05) and associated with longer progression-free survival and overall survival (both P < 0.05). The genes related to B cells, B cell functions, and T cell functions were up-regulated in patients with CB compared to that with non-CB (all P < 0.05). Naïve B cells and plasma cells were significantly increased in patients with CB (both P < 0.05). The expression levels of stromal CD20 by IHC trended to increase in patients with CB ( P = 0.08). Conclusions: B cells in tumor microenvironment may be associated with CB of anti-PD-1/PD-L1 therapy in patients with ESCC. (Funded by MOST 105-2314-B-002 -186 -MY3; MOHW107-TDU-B-211-114017; MOST 108-2314-B-002 -076 -MY3; MOST 107-2314-B-002-199 -).