bluuebunny/crossref_metadata_2025_split huggingface dataset:
Definitive chemoradiotherapy +/- induction chemotherapy in esophageal cancer: A real-world experience.
Authors: Matoska Thomas , Jurkowski Lauren , Banerjee Anjishnu , Shreenivas Aditya V. , Shukla Monica , Martinez Enrique , Kodali Divya , Linsky Paul , Gasparri Mario , Chakrabarti Sakti , George Ben , Gore Elizabeth , Johnstone Candice Aitken , Johnstone David , Puckett Lindsay 
Published: June 2022

e16072 Background: The SEER 5-year overall survival rate for all stages of esophageal cancer (EC) was 25% in 2019. Definitive chemoradiation (CRT) remains the primary treatment approach for locally advanced EC in the US, however, there are data to support use of induction chemotherapy (CT) in addition to CRT, particularly in adenocarcinoma (AC) histology. The purpose of our study was to assess outcomes in EC patients treated with definitive CRT (+/- induction) to determine which prognostic factors predicted for better survival in a recent, real-world cohort of patients, including those with limited stage IV disease. Methods: This retrospective study included Stages II-IVB (AJCC 8th ed.) EC patients treated with definitive CRT (radiation dose of ≥40 Gy and at least two cycles of concurrent CT [+/- induction CT, +/- esophagectomy]) at our institution between 2008 and 2020. To analyze prognostic factors and estimate OS, univariate models (UVA) and a multivariate (MVA) Cox proportional hazards regression model including age, Stage (II, III, IVA, IVB), AC vs. SCC, esophagectomy, ECOG performance status (PS), and induction CT were performed. Results: Of the 183 patients treated with definitive CRT, 18 were stage II, 119 stage III, 21 stage IVA, and 25 stage IVB. There were 45 SCC and 138 AC patients (Table). Prognostic factors associated with prolonged OS on MVA included lower PS (p<0.01) and esophagectomy (p = 0.05). Stage IVA was associated with shorter survival (p<0.01). Induction CT (delivered in 53% of AC, 31% SCC) was associated with improved survival on UVA (p=0.04), but not MVA (p = 0.08). By histology, 5-year survival rate was 42.7% and 18.2% for AC and SCC, respectively. Conclusions: At our institution, those who received an esophagectomy and those with lower ECOG scores had better survival. The 5-year survival rate was higher for AC patients compared to SCC, with more AC patients receiving esophagectomy and induction CT (significant on UVA, but not MVA). The 5-year survival rate for AC in our study was nearly identical to that seen in the CROSS trial (Shapiro et al. 2015) AC cohort but included >25% stage IV patients. This modern cohort also included poor PS (ECOG≥2) patients (9.2% AC and 13.6% SCC), suggesting induction CT, in addition to pre-operative CRT + surgery, may have added benefit in a real-world practice. Thus, further prospective study is needed.[Table: see text]
Camrelizumab in combination with fluorouracil or taxol plus platinum chemotherapy as first-line treatment of esophageal squamous cell carcinoma: A multicenter, open-label, prospective cohort study.
Authors: Zhao Jun , Hu Wenqing , Zhang Xiaoling , Du Yunyi , Yao Chunmei , Ma Ning , Yang Wei , Yang Bo , Xue Yudong , Gao Yangjun , Wang Yu , Liu Min , Wang Mei , Wang Hui , Feng Tingting , Cai Linlin , Zhang Cuihua , Ma Kai , Xu Ning , Lu Jing 
Published: June 2022

e16084 Background: The introduction of immune checkpoint inhibitors (ICIs) after chemotherapy and targeted therapy has altered the treatment pattern of esophageal squamous cell carcinoma (ESCC). However, using ICIs alone results in a poor response rate. Fortunately, fundamental research indicates that chemotherapy might trigger immunogenic death of tumor cells by releasing tumor antigens, hence eliminating immune system repression of tumor cells. On this basis, a number of clinical studies, including KEYNOTE-590, CheckmMate-648, ORIENT-15, and ESCORT-1st, on the first-line treatment of ESCC with ICIs coupled with chemotherapy, including fluorouracil or taxol and platinum (PF or TP), were conducted and yielded favorable results. However, the advantage of safety and effectiveness of ICIs combination with PF and TP in Chinese ESCC remains unknown. Furthermore, since the southeast part of Shanxi province has a high prevalence of esophageal cancer, the geographical features of ESCC patients will be examined. Methods: Camrelizumab was maintained after 6 cycles of camrelizumab in combination with PF or TP chemotherapy. From May 2020 to February 2022, our study has included 40 locally progressed and advanced ESCC patients. Camrelizumab was administered in combination with PF to 11 patients and TP to 29 patients. Every 6 weeks, efficacy was examined using RECIST 1.1, and 33 patients were evaluated. This research was registered with the Chinese Clinical Trials Registry (ChiCTR2000037942). Results: The median treatment time was 5.8m. 82.5% (33/40) patients were availably evaluated. The objective response rate (ORR) was 72.7% (24/33) and the disease control rate (DCR) was 97.0% (32/33). There is no statistically significant difference in ORR ( p=0.1779) and DCR ( p=0.1005) between PF and TP (55.6% vs 79.2%, 88.9% vs 100%) regimens. At this moment, mPFS has not been achieved. The most common adverse events (AEs) were anemia (22.5%, 9/40), lymphocytopenia (15%, 6/40), neutropenia(15%, 6/40), reactive cutaneous capillary endothelial proliferation (RCCEP) (12.5%, 5/40) and fatigue (7.5%, 3/40). Thrombocytopenia (2.5%, 1/40), neutropenia (2.5%, 1/40) and leukopenia (2.5%, 1/40) were the most common grade 3 or 4 toxicities The most frequently reported immune-related AEs were RCCEP (12.5%, 5/40) and hypothyroidism (7.5%, 3/40). There were no new significant adverse events. Conclusions: Camrelizumab in combination with chemotherapy is a promising regimen with good tolerability in the first-line treatment of ESCC. Compared with FP, TP had more therapeutic advantages, But the result is a stage summary, and further observation is needed. Clinical trial information: ChiCTR2000037942. [Table: see text]
Molecular profile of exosomal miRNA differential expression in ascites of untreated advanced gastric cancer patients with peritoneal metastases.
Authors: Wu Yi , QI Changsong , Gao Jing , Chong Xiaoyi , Shen Lin 
Published: June 2022

e16086 Background: The incidence of gastric cancer is high, and the proportion of peritoneal metastases among patients with early-stage operable gastric cancer is about 10%-20%, while the proportion of peritoneal metastases among patients with stage 3 (stage III) gastric cancer is as high as 40%. The prognosis of gastric cancer patients with peritoneal metastases is poor, with a median survival of 7 months. Exosomes are considered to be carriers of intercellular communication and abundant miRNAs (miRNAs) are enriched in patients' ascitic fluid exosomes. Methods: Ascites exosomes were characterized according to ISEV2018. The pro-tumor proliferation and metastatic ability of ascites exosomes in gastric cancer patients with peritoneal metastases was observed by small animal in vivo imaging. Six untreated ascites exosomes from gastric cancer patients with peritoneal metastases were selected for miRNA sequencing with five ascites exosomes from patients with benign disease to determine differentially expressed molecular profiles. The target mRNAs of selected miRNAs were predicted by miRhybrid, TargetScan database, and enriched in KEGG database for the function of target mRNAs. Results: Compared to ascites exosomes from patients with benign disease, or ascites exosomes removed from gastric cancer patients with peritoneal metastases, ascites exosomes from gastric cancer patients with peritoneal metastases had a significant contribution to tumor proliferation and metastasis. Among them, molecules such as miR-196 were expressed up-regulated in all six samples of gastric cancer peritoneal metastasis group, and the difference was significant. The target mRNAs of differentially expressed miRNAs were associated with motility, adhesion, stromal degradation, hypoxia tolerance, apoptosis, and angiogenesis (biological behaviors involved in this process of gastric cancer peritoneal metastasis). Conclusions: Molecules such as miR-196 are important for the clinical problem of peritoneal metastasis of gastric cancer and can be used as biomarkers for disease assessment and potential therapeutic target.
Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach.
Authors: Zhu Mengxuan , Chen Erbao , Yu Shan , Xu Chen , Yu Yiyi , Cao Xin , Li Wei , Zhang Pengfei , Wang Yan , Cui Yuehong , Li Qian , Liu Tianshu 
Published: June 2022

e16094 Background: Hepatoid adenocarcinoma (HAC) is a rare pathological subtype of extrahepatic tumor, featured by hepatoid differentiation and α-fetoprotein (AFP)-production. Hepatoid adenocarcinoma of the stomach (HAS), accounting for 0.17 to 15% of gastric cancers, is the most common subtype of HAC, and has attracted increasing attention duo to its high degree of malignancy. Compared with classic gastric cancer (GC), HAS showed a higher rate of vascular invasion, lymph node metastasis, and liver metastasis, with only 9% survival at 5 years. In this study, we aim to investigate the molecular features of HAS and identify the potential therapeutic targets for HAS. Methods: We conducted whole-exome sequencing (WES) of 40 paired tumor and normal samples, including 25 HAS, 6 HAC of other organ and 9 AFP-producing gastric cancer (AFPGC). All patients underwent radical surgery at Shanghai Zhongshan Hospital between July 2013 and September 2017. qRT-PCR, Western blot and immunohistochemistry were detected to explore MUC19 expression in HAS. CCK8 assay, Transwell assay, immunofluorescence assay and subcutaneous xenograft tumor model were used to detect functional effects and the mechanism of MUC19. Results: In HAS patients, the top 5 frequently mutated genes were TP53 (44%), TTN (44%), MUC19 (40%), CCNE1 (28%) and CDC27 (28%). Further compared with TCGA datasets, MUC19, CCNE1, CDC27 mutations were almost undetectable in STAD, CRC and HCC. In terms of CNV analysis, VSTM2B, PLEKHF1, POP4, URI1 and TERT were the most frequently amplificated genes in HAS tumor tissues. Interestingly, amplification of 4 genes (VSTM2B, CCNE1, LEKHF1, POP4), which located in chr19q12, was significantly associated with poor prognosis. The tumor mutational burden (TMB) levels and AFP expression of HAS and AFPGC patients were no significantly different, while patients with higher TMB had a remarkably longer overall survival ( p= 0.0065). Moreover, we found MUC19 expression was positively correlated with AFP levels in HAS and MUC19 promoted the transcription of AFP in GC cells. Mechanistically, MUC19 contributed to the aggressive malignancy phenotypes of GC cells through activating the Wnt/β-catenin signaling pathway. Conclusions: MUC19 may be a potential target for HAS diagnosis and treatment. Amplification of genes located in chr19q12 occurred frequently in HAS and were associate with poor prognosis. TMB was sensitive for the overall survival of HAS patients.
Does hyponatremia predict worse outcomes in gastric cancer?: A nationwide study.
Authors: Franco Jorge , Franco Diana , Farooq Umer , Ma Irene 
Published: June 2022

e16098 Background: Hyponatremia has historically been reported to increase mortality and length of stay in hospitalized patients with solid tumors. There are sparse reports of hyponatremia linked to gastric cancer in the published literature. Therefore, we evaluated mortality, morbidity, and resource utilization in gastric cancer patients secondary to hyponatremia. Methods: We investigated the National Inpatient Sample 2019 employing International Classification of Diseases-10 (ICD-10) codes to include adult patients with gastric cancer. Effect of hyponatremia was studied on mortality, morbidity, and resource utilization. Analyses were performed using STATA (v 14.2), considering 2 sided P< 0.05 as statistically significant. Proportions were compared using Fisher exact test and continuous variables using Student’s t-test. Confounding variables were adjusted using multivariate logistic and linear regression analyses. These included: gender, race, Charlson Comorbidity Index, chronic kidney disease, congestive heart failure, cirrhosis, nephrotic syndrome, hypothyroidism, adrenal insufficiency, alcohol use disorder, and admission for hypovolemia or psychogenic polydipsia and various patient and hospital characteristics. Results: Out of 43,015 patients with gastric cancer in 2019, 13.59% (5,845) had hyponatremia on presentation (Table. 1). Patients with hyponatremia had 12.23% in-hospital mortality, while 6.69% for patients without hyponatremia. After adjusting for confounders, hyponatremia imparted higher odds of mortality (Adjusted odds ratio (aOR) for mortality 1.89, 95% confidence interval (CI): 1.54–2.32, P< 0.01). Hyponatremia also resulted in higher resource utilization marked by the length of stay, hospital charges, and ICU admission (higher mean LOS by 2.09 days, higher mean total hospital charges by $22,320, and higher odds of ICU admission). In addition, patients with hyponatremia had higher odds of acute renal failure (aOR 2.38, 95% CI: 2.05–2.77, P< 0.01). Rates of cerebral edema and altered mental status were equal between the two study groups ( P> 0.05). Conclusions: Hyponatremia in gastric cancer patients had a prevalence of 13.59% and resulted in increased in-hospital mortality. Whether time-efficient treatment of hyponatremia would help reduce mortality and improve outcomes remains to be determined in future studies.[Table: see text]
Serum cytokines could be predictors for PD-1 antibody response in advanced HBP cancer.
Authors: Mei Shengmin , He Zenglei , Wang Bin , Xue Liang , Xu Li , Ling Qi 
Published: June 2022

e16114 Background: According to previous clinical trials and pilot studies, PD1 antibodies might provide favorable long-term survival in combination with chemotherapy for unresectable hepatobiliary and pancreatic (HBP) cancers. We conducted a real-world evaluation of PD1 antibodies in patients with unresectable HBP cancers. We also aimed to explore biomarkers for the early prediction of PD1 antibodies response. Methods: From Jan 2021 to Dec 2021, 48 unresectable HBP cancers were enrolled in Yuhang campus, the first affiliated hospital, Zhejiang university school of medicine. The key eligibility criteria were:(1)histopathologically confirmed advances unresectable HBP cancers; (2)without systematic treatment; (3)¡Ý18 years old; (4)ECOG PS 0 or 1. Clinical decisions were made by multi-disciplinary team (MDT). The treatment efficacy was evaluated by mRECIST. Results: A total of 48 patients were finally included and analyzed, which their baseline characteristics were listed in Table. we assessed the treatment efficacy using the dynamic change of tumor makers. And we observed that tumor markers of progressive disease(PD) group were higher than those of stable disease(SD) and partial response(PR) group. A total of 37 patients with complete biomarker data, were finally included in cytokines and immune response analysis. During the immune checkpoint inhibitors treatment, we detect the trough concentration of serum cytokines(IL-2, IL-4, IL-6, IL-10, IL-16, TNF-¦Á and TIFN-¦Ã). We observed that serum cytokines indexes of PD group were higher than those of SD and PR group. Conclusions: We observed that tumor markers of PD group were higher than those of SD and PR group. The serum cytokines (IL-4, IL-16 and TIFN-¦Ã) may be potential biomarkers for the early prediction of PD1 antibodies response. [Table: see text]
Update results from ALTER-H004 study: Anlotinib combined with TACE as adjuvant therapy in hepatocellular carcinoma patients at high risk of recurrence after surgery—A single-arm, multicenter, phase II clinical trial.
Authors: Wu Zheng , Wang Zheng , Zhang Lei , Song Xiaojing , Du Xilin , Tan Kai 
Published: June 2022

e16120 Background: Hepatectomy is considered to be an effective curative treatment for hepatocellular carcinoma (HCC), however, high recurrence rate after curative resection severely reduces the long-term survival of HCC patients (pts). Transarterial chemoembolization (TACE) as adjuvant therapy has been proved to improve clinical outcomes for pts with high recurrence risk factors after hepatectomy, but the effect is still unsatisfactory. ALTER-H004 trial was designed to evaluate the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. Here we updated the results at the data cutoff of January 20, 2022. Methods: This single arm, multicenter, phase II trial of ALTER-H004 was planned to enroll 30 pts which with histologically confirmed HCC and undertook hepatectomy within 1-2 months. The recruited pts who did not recieve any previous tumor-related treatment must have any of the following high risk factors: ≥5 cm and < 10 cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II). Eligible pts received conventional TACE treatment within 1-2 months after hepatectomy. On the 3-5th day after TACE treatment, oral anlotinib (12mg, qd, d1-d14, q3w) was given until disease recurrence or unacceptable toxicity. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: By the cutoff date of January 20, 2022, 26 pts were enrolled and 25 pts received at least once tumor assessment. According to RECIST 1.1, 14 of 25 did not progress were still on treatment and 7 relapsed. One withdrew the consent and 3 discontinued because of intolerable adverse events. The longest duration of treatment is 16.53 months. The DFS were not mature and the 6-month DFS rates were 77.45% (95% CI: 53.83̃89.99). 12 of 25 pts (48.0%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 pts (20.0%) included hypertension (8.0%), leukocytopenia (8.0%) and ascites (4.0%). No grade 4 or 5 TRAEs occurred. Conclusions: The update results suggested that anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited promising clinical benefit and favorable safety profile, and the results needed to be confirmed in trials continued subsequently. Clinical trial information: NCT04213118.
Feasibility of disease recurrence monitoring in liver post-transplantation for patients with hepatocellular carcinoma via personalized and tumor-informed ctDNA test.
Authors: Abdelrahim Maen , Esmail Abdullah , Saharia Ashish , McMillan Robert , He Aiwu Ruth , Starr Jason S. , Dhani Harmeet , Aushev Vasily N. , Koyen Malashevich Allyson , Rattigan Nicole Hook , Gauthier Phil , Jarudi Adham , Ghobrial Rafik Mark 
Published: June 2022

e16123 Background: Hepatocellular carcinoma (HCC) is an aggressive malignancy for which liver transplantation can be curative. Unfortunately, ̃8-20% of HCC patients will go on to relapse post-transplantation. Personalized and tumor-informed circulating tumor DNA (ctDNA) testing (Signatera, bespoke mPCR NGS assay) has been validated to accurately predict relapse across solid tumors, ahead of radiological imaging. Here, we demonstrate the feasibility of ctDNA testing for monitoring relapse in HCC patients who underwent liver transplantation with curative intent. Methods: A total of 10 HCC patients, stage I-IV, who underwent curative liver transplantation with longitudinal ctDNA monitoring were included in the analysis. Alpha-fetoprotein (AFP) levels and images were measured during surveillance in a subset of patients. Results: In this cohort of 10 patients, 2 (20%) tested ctDNA positive during surveillance, both of whom relapsed. Of these, one tested ctDNA positive two months prior to imaging. Of the 8 patients who did not test ctDNA positive during surveillance, all remained disease-free by imaging. Two patients had elevated AFP, neither of whom relapsed. Of the 2 patients who relapsed, AFP levels were available for one patient and fell within the normal range. Conclusions: Our study illustrated the feasibility of performing longitudinal ctDNA assessment in patients with HCC (post-transplantation) during surveillance. ctDNA status but not AFP was associated with recurrence and was able to inform disease status ahead of imaging. To facilitate clinical decision-making, specifically with adjuvant therapy and immunosuppression management, additional studies with larger patient cohorts will be needed to validate the clinical utility of ctDNA testing in HCC.
B-catenin mutations and the response of advanced hepatocellular carcinoma to immune checkpoint inhibitors.
Authors: Mahadevia Himil , Imperial Robin John Lester , Toskich Beau , Mody Kabir 
Published: June 2022

e16124 Background: Immune checkpoint inhibitors (ICI) have emerged as a standard treatment option for advanced hepatocellular carcinoma (HCC). Unfortunately, many patients with advanced HCC develop progressive disease on ICI therapy. Furthermore, clinical predictors of response to ICI therapy in HCC are poorly understood. B-catenin mutations are among the most frequent genetic abnormalities in HCC and may provide a mechanism for immune evasion and poor response to ICI (Ruiz de Galarreta, Marina et al. “β-Catenin Activation Promotes Immune Escape and Resistance to Anti-PD-1 Therapy in Hepatocellular Carcinoma.” Cancer discovery 9,8 (2019): 1124-1141. doi:10.1158/2159-8290.CD-19-0074). Methods: We conducted a retrospective cohort study of patients with advanced HCC who were treated with ICI therapy. All patients had ctDNA tumor profiling and were assessed for B-catenin mutation status. Disease status was determined by RECISTv1.1. Median progression-free survival (PFS), 3-month PFS, 6-month PFS, and the disease control rate (DCR) on ICI therapy were compared between B-catenin mutation (BCM) and B-catenin wild-type (BCWT) groups. Results: 15 stage III/IV HCC patients were included in the study. 9 patients harbored BCMs and 6 patients were BCWT. The median PFS in patients with BCM HCC was 4.0 months versus 4.9 months in patients with BCWT HCC. At 3 months, PFS was 56% for BCM HCC compared to 67% for BCWT HCC. Furthermore, the 6-month PFS was 11% for BCM HCC and 50% for BCWT HCC. For best response, 33% of patients with BCM HCC achieved stable disease compared to 67% of patients with BCWT HCC. No patients in our cohort achieved partial or complete response. The DCR for BCM HCC was 33% and the DCR for BCWT HCC was 67%. Conclusions: In patients with advanced HCC, B-catenin mutation status may serve as a potential biomarker of response to ICI therapy. Our data suggests that patients who do not harbor these mutations, have a more durable response to ICI therapy. Further studies are needed to validate these findings.