bluuebunny/crossref_metadata_2025_split huggingface dataset:
COVID-19 infections among minority patients with gastrointestinal malignancies in urban safety net academic medical centers.
Authors: Gali Radhika , Viteri Malone Mariuxi Alexandra , Goel Sanjay 
Published: June 2022

e15610 Background: COVID 19 infection has worse outcomes and is more severe among frail patients and with co-morbidities. Additionally, it was suggested by Mehta et al that gastrointestinal malignancies may have worse outcomes. Based off these findings, we have evaluated outcomes and potential predictors of these outcomes in patients with gastrointestinal malignancies and COVID 19 infection. Methods: We conducted a retrospective evaluation of 69 cases of patients between February 2020 to February 2021, that had both COVID 19 infection and a gastrointestinal malignancy, including: gastric, colon, pancreatic, biliary, and hepatic. We studied population general characteristics, most common tumors, oxygen requirements, management and death frequencies, at two urban safety net hospitals. Results: The median age of patients with gastrointestinal malignancies and COVID-19 infection was 68 (33 to 87), it was more frequently seen among males (N = 46, 67%); patients had on average 1-7 other comorbidities (N = 55, 80%), hypertension being the most common (N = 43, 62%). All patients in this study were minorities, the majority being Hispanics (N = 32, 46%), followed by African Americans (N = 21, 30%), the rest of patients were minorities such as Asians, Native Americans, and others (N = 16, 23%). We noted that more than half of patients were obese (N = 24, 35%), or overweight (N = 19, 28%), with a mean BMI of 26.24. Most patients were non-smokers (N = 39, 57%). The performance status among these patients was excellent in the large majority (ECOG 0-2; N = 62, 90%). The majority of malignant tumors were adenocarcinomas (N = 63, 91%); others included neuroendocrine tumors (N = 4, 6%) and gastrointestinal tumors (N = 2, 3%), the majority were advanced stage disease between stage III to stage IV disease (N = 38, 55%). The most common malignancy was colon cancer (N = 44, 64%), and also was the most reported deaths were among patients those patients with colon cancer (N = 13, 57%). Among patients that needed to be hospitalized (N = 43, 62%), needed some sort of oxygen supplementation (N = 36, 84%), a small number of patients required ICU admission (N = 8, 19%). When hospitalized, patients were mostly treated with hydroxychloroquine (N = 30, 70%) and steroids (N = 7, 16%). Inflammatory markers such as D-dimer, ferritin, C-RP were not reported in the majority of cases. Overall, the case fatality rate across all gastrointestinal malignancies was noted to be substantial (N = 22, 32%), 35% in males and 26% among females (p = 0.46). Conclusions: During the first year of the COVID-19 pandemic, patients with gastrointestinal malignancies who were infected, seemed to have a high chance to be admitted to the hospital (62%), once hospitalized the majority required some sort of oxygen supplementation (84%) and had a high case fatality rate from the COVID-19 infection (32%).
A real-world assessment of genomic testing and treatment in stage 4 gastric cancer patients.
Authors: Conner Therese , Arguello Roy , Loaiza-Bonilla Arturo , Hauser Robert S , Harris Barbara , Cruz Jackeline 
Published: June 2022

e16007 Background: In gastric cancer, genomic testing plays an important role in treatment decisions that could improve response and extend life. While advanced therapies are recommended for certain patients, little is known about the frequency of real-world testing and treatment in metastatic disease. This study sought to assess the incidence and results of genomic testing among metastatic gastric cancer patients in the United States. Methods: This retrospective study used de-identified electronic health record data from adult Stage 4 gastric and gastroesophageal junction (GEJ) adenocarcinoma patients who received treatment at Cancer Treatment Centers of America (CTCA) from 2016-2021. Results: Among 238 patients, 172 had gastric and 67 had GEJ cancer. Mean age at diagnosis was 56 years (SD = 10.5), 64% were male, and 68% were Caucasian. Of 238, 101 (42%) received genomic testing at CTCA, 113 days (median) post-diagnosis. 49 (21%) were HER2+; 89 (37%) had PD-L1 testing, of which 67 (75%) were > 1%. Four (2%) had tumor mutation burden (TMB) >10 (high). Among 48 (20%) patients who received trastuzumab, 85% started in 1st line, and 97% of cycles were combination therapy. Of the 33 patients who received pembrolizumab, 97% started in 2nd line; 79% started prior to 2020 and 94% of cycles were monotherapy. Conclusions: In stage 4 gastric cancers, this study found that almost half of patients received genomic testing within the first year of diagnosis. Percentages of patients with gene amplification were within ranges of similar studies. Timing of trastuzumab and pembrolizumab was in accordance with guidelines. Most patients initiated pembrolizumab prior to 2020, suggesting early adoption of use. Cost-utility analyses of treatment options may be warranted in future research.[Table: see text]
Effect of deep neuromuscular block on surgical pleth index-guided remifentanil administration in the elderly undergoing laparoscopic gastrectomy for gastric cancer.
Authors: Kim Ji Eun 
Published: June 2022

e16048 Background: Deep neuromuscular block (NMB) has been increasingly utilized in laparoscopic oncologic surgery, but its role in reducing intraoperative opioid requirement has yet to be investigated. Opioid in cancer patients is related with immunosuppression. Surgical pleth index (SPI) quantifies nociception. We investigated the effects of deep NMB on remifentanil requirements in the elderly patients undergoing laparoscopic gastrectomy under SPI-guided anesthesia. Methods: In this randomized controlled trial, the elderly patients aged 60–85 years who underwent laparoscopic gastrectomy for gastric cancer were included. Arrythmia, peripheral vascular disease and chronic opioid user were excluded. The patients (n = 60) were randomly allocated into deep (n = 30) or moderate (n = 30) NMB groups between December 2019 and December 2020. The moderate NMB group was maintained as Train-of-four count 1-2 during surgery and revered using neostigmine 50 ug/kg after the end of surgery. The deep NMB group was maintained as post-tetanic count 1-2 and reversed with using sugammadex 4 mg/k. The remifentanil dose was assessed during intubation, from skin incision until CO2 insertion, and pneumoperitoneum. Results: Demographic, hemodynamic and operational data were similar between two groups, except rocuronium dose. The remifentanil doses administered for tracheal intubation and during time from skin incision until CO2 insertion were similar (P = 0.412 and P = 0.649). In addition, total dose of remifentanil administered during pneumoperitoneum was not significantly different between two groups (P = 0.315), which remains non-significant when adjusted by weight, duration or both (P = 0.603, P = 0.146, and P = 0.389). Consequently, total dose of remifentanil administered during anesthesia was not different (P = 0.247). In post-anesthesia care unit, the pain score and the number of patients receiving analgesics were not different (P = 0.064 and P = 0.773). However, the duration of post-anesthesia care unit stay was significantly lower in the deep NMB group compared with in the moderate NMB group (P = 0.011). Conclusions: Deep NMB did not reduce the remifentanil requirement compared with moderate NMB in the elderly patients undergoing laparoscopic gastrectomy under SPI-guided anesthesia. Clinical trial information: NCT04205097.
A systematic review and meta-analysis to evaluate the efficacy and safety of nivolumab for advanced esophageal, gastroesophageal, and gastric cancer.
Authors: Oyenuga Mosunmoluwa , Mohamed Mohamed G , Sartaj Sara , Patel Rushin , Lacasse Alexandre , Mehta Mudresh , Sen Sandeep 
Published: June 2022

e16060 Background: Esophageal, gastroesophageal, and gastric cancers make up about 1% of the cancer cases in the United States and most patients are diagnosed at advanced stages. Despite treatment options available, these patients have a median survival of about one year. Due to the advancement in treatment using immune checkpoint inhibitors in cancer therapy, this class of medications were recently approved for their use in patients with esophageal, gastroesophageal, and gastric cancer. A literature review and meta-analysis was conducted to evaluate the efficacy and safety of use of nivolumab in these group of patients. Methods: We systematically searched multiple databases using pre-specified search terms. We included only RCTs comparing Nivolumab with/without chemotherapy versus chemotherapy, in patients with advanced esophageal, gastroesophageal, or gastric cancer. Co-primary outcomes were overall survival (OS) and progression free survival (PFS). We also reported response rates, sensitivity analysis and adverse effects (AE), using fixed effects model via RevMan 5.4 software. Results: Three RCTs were included with a total of 2,645 patient and a median follow-up of 13 months. The patients’ mean age was 62±22 years, 75% were males, 79% were stage IV metastatic disease, and 29% had ≥1% PD-L1 expression. Compared to the chemotherapy group, Nivolumab group had a significantly favorable OS and PFS [HR 0.78;95% CI (0.69, 0.87), P < 0.001], [HR 0.83;95% CI (0.75, 0.92), P < 0.001] respectively. Sensitivity analysis showed significant effect of Nivolumab only in patients with ≥1 % PD L1 expression [HR 0.71; 95% CI (0.64, 0.80), P < 0.001]. Chemotherapy group had a significantly favorable outcome regarding serious AE [OR 1.57;95% CI (1.28, 1.93), P < 0.001], and diarrhea [OR 1.29;95% CI (1.07, 1.56), P = 0.007], with no difference regarding AE leading to death [OR 1.75;95% CI (0.88, 3.47), P = 0.11]. Conclusions: The use of nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers is associated with improved disease-free survival and overall survival compared to treatment with chemotherapy, albeit at an increased risk of serious adverse effects. The improvement in survival was significant in patients with ≥1% PD L1 expression.
Linkage of time interval from neoadjuvant chemoradiotherapy to surgery with pathological response and survival profile in resectable esophageal cancer patients.
Authors: Liu Jiaqi , Zeng Xiaoxiao , Zhou Xiaojuan , Xu Yong , Ding Zhenyu , Hu Yang , Yuan Yong , Chen Longqi , Wang Jin , Lu You , Liu Yongmei 
Published: June 2022

e16071 Background: The optimal time interval from neoadjuvant chemoradiotherapy (nCRT) to surgery remains controversial in esophageal cancer (ESC) patients. Hence, this study aimed to evaluate the relationship of the time interval from nCRT to surgery with the prognosis in ESC patients. Methods: Totally, 166 ESC patients treated with nCRT followed by surgical resection were reviewed. Their pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS) were analyzed. Based on the median duration from nCRT to surgery, patients were classified into duration from nCRT to surgery ≥66 days group or <66 days group. Results: The pCR rate was elevated in duration from nCRT to surgery ≥66 days group compared to <66 days group (48.3% vs. 25.3%, P = 0.002), while DFS ( P = 0.316) and OS ( P = 0.883) were of no difference between these two groups. The duration from nCRT to surgery (≥66 days vs. <66 days) (odds ratio (OR): 2.149, P = 0.039) was independently related to improved pCR rate as validated by multivariate logistic regression, while it did not correlate with DFS or OS (both P > 0.05) by univariate and multivariate Cox’s regression analyses. Moreover, female gender ( P=0.001) and radiation dose ≥40 Gy. ( P = 0.039) could independently predict better pCR rate; and pCR rate was independently related to longer DFS ( P = 0.003) and OS ( P = 0.008). Conclusions: The prolonged time interval from nCRT to surgery relates to a higher pCR rate but does not correlate with DFS or OS in ESC patients.
The analysis of CCND1 amplification in Chinese patients with esophageal carcinoma.
Authors: Liu Lianke , Xu Fang ye , Xu Jiali , Sun Wei jie , He Yuange , Shao Qianwen , Wang Ting 
Published: June 2022

e16073 Background: The CCND1 gene is considered an oncogene located on human chromosome 11q13.3, Cyclin D1 protein encoded by the CCND1 gene is the critical gatekeeping protein in charge of regulating the transition. Previous studies have reported that CCND1 amplification associated with a negative response to immune checkpoint inhibitors (ICIs) in pancancers, but the association with clinical and molecular characteristics in esophageal carcinoma (ESCA) have not been researched. Herein, we explore CCND1 amplification profiles in Chinese patients with ESCA. Methods: A total of 59 patients of ESCA with paired tumor-normal samples were collected into the study. All samples were detected by DNA based sequencing with a 1021 gene panel. Results: Firstly, the frequency of CCND1 amplification in Chinese ESCA patients was 32.20% (19/59). Then, all the samples were divided into two groups according to whether CCND1 was amplified or not. In the CCND1 amplification group, the top8 co-mutated genes were TP53, FGF4, FGF3, FGF19, MYC, NOTCH1, CDKN2A, CDKN2B. We calculated the clinical and molecular characteristics between the two groups, the results showed there were no difference in gender, age and TNM stage. Meanwhile, the CCND1 amplification group had more somatic mutations (median 19 vs. 11, P = 0.0003), higher TMB value (median 8.64 vs. 5.76, P = 0.0199) and more TMB-H patients (47.37% vs. 17.50%, P = 0.018). Indicating the CCND1 amplification is associated with TMB-H in ESCA. However, previous studies have reported the negative impact of CCND1 amplification on the efficacy of ICIs in pancancer (including ESCA), these results suggesting the efficacy of ICIs in ESCA may be affected by multiple biomarkers, especially for TMB-H patients should be concerned about the high frequency CCND1 amplification, the patients may have a poorer benefit from immunotherapy. Conclusions: The efficacy of ICIs in ESCA may be affected by multiple biomarkers, especially for TMB-H patients should be concerned about the higher frequency of CCND1 amplification, these patients may have a poorer benefit from immunotherapy.[Table: see text]
Ramucirumab as second-line treatment in patients with advanced hepatocellular carcinoma (HCC) and elevated alpha-fetoprotein (AFP) following first line sorafenib: Pooled efficacy and safety in Chinese patients across two global randomized phase 3 studies (REACH-2 and REACH).
Authors: Shao Guoliang , Bai Yuxian , Chen Xiaoming , Gu Shanzhi , Gu Kangsheng , Yuan Xianglin , Widau Ryan C , Zhang Wanli , Zhang Qiang , Qin Shukui 
Published: June 2022

e16081 Background: REACH-2 and REACH were two global, randomized, double-blind, placebo (PL)-controlled phase 3 studies of Ramucirumab (RAM) versus PL in patients with HCC after prior sorafenib. REACH-2 confirmed the RAM treatment benefit for patients with baseline AFP ≥ 400 ng/mL, consistent with results in a prespecified subgroup of patients in REACH with AFP ≥ 400 ng/mL. A pooled analysis was performed to evaluate the efficacy and safety of RAM in Chinese patients (including patients from mainland China, Hong Kong, and Taiwan) from REACH-2 and REACH with baseline AFP ≥400 ng/mL. Methods: Except for AFP level requirement, REACH-2 and REACH were similar in study design and included patients who had advanced HCC (BCLC stage C or B disease refractory or not amenable to locoregional therapy), Child-Pugh A, ECOG PS 0-1, and prior sorafenib. Patients were randomized to RAM (8 mg/kg) I.V. or PL Q2W, plus best supportive care, until disease progression or unacceptable toxicity. Individual patient data were pooled from REACH-2 and REACH (AFP ≥400 mg/mL). Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier method and Cox proportional hazard model. Objective response rate (ORR), disease control rate (DCR), and safety were reported. Efficacy analyses were stratified by study to account for any potential difference in the two studies. Results: Data from 155 Chinese patients were pooled from REACH (51) and REACH-2 (104) (N = 98 RAM vs N = 57 PL). Baseline characteristics were generally balanced between arms in pooled data set; however, lower median level of AFP was noted in the RAM arm. In the pooled population, RAM treatment numerically improved OS over PL (median OS 7.1 months vs 4.7 months; HR = 0.735 [95% CI: 0.512, 1.055]). Improvements in PFS (median PFS 2.6 months vs 1.5 months; HR = 0.666 [95% CI: 0.459, 0.967]), ORR (3.1% vs 0%), and DCR (44.9% vs 29.8%) were also observed. Hypertension (6.1% vs 1.8%), pneumonia (5.1% vs 1.8%), and hyponatremia (5.1% vs 1.8%) were the Grade ≥3 treatment-emergent adverse events (TEAEs) among ≥ 5% patients that was more frequently observed in the RAM arm compared with the PL arm. Conclusions: Pooled analysis of two phase 3 trials of RAM as second-line treatment in patients with HCC following sorafenib demonstrated a clinically meaningful benefit with a manageable safety profile in Chinese HCC patients with baseline AFP ≥ 400 ng/mL. Treatment benefits in OS observed in the pooled Chinese population were consistent with the entire population from REACH/REACH-2 (AFP ≥ 400 ng/mL). Clinical trial information: NCT01140347, NCT02435433.
Mutational landscape of DNA damage response deficiency-related genes and its association with immune biomarkers in esophageal squamous cell carcinoma.
Authors: Xu Fei , Chen Zhiming , Chen Gang , Zhu Yongjun , Chen Ji , Miao Feng , Wu Ning , Yang Song , Mao Beibei , Wang Shengzhou 
Published: June 2022

e16100 Background: Esophageal squamous cell carcinoma (ESCC) has limited effective treatment strategies. DNA damage response (DDR) genes are of therapeutic interest in multiple cancer types. This study aimed to depict the landscape of DDR mutations in ESCC and evaluate the association between DDR mutations and known immunotherapy biomarkers. Methods: We recruited 250 Chinese patients with ESCC and performed next-generation sequencing. The DDR status definition was based on the mutational status of any of the 25 DDR core genes. A total of 107 patients underwent a PD-L1 examination. PDL1-H was defined as CPS ≥10. Results: Among the 250 patients, 73 (29.2%) harbored at least one DDR gene mutation and were defined as DDR-mut. Among the six functional DDR pathways, homologous recombination (HR) (12.4%, 31/250) and others (11.6%, 29/250) were the most frequently mutated. DDR-mut patients were significantly associated with higher tumor mutational burden than those in the DDR-wt group ( P = 7.4e-07). Patients with PDL1-H accounted for 21.2% (36/107) of the patients. PDL1-H was more prevalent in DDR-mut than DDR-wt, although the P value did not reach a significant level (40.5% vs. 30%, P = 0.29). Further analysis revealed that BRCA1, one of the most frequently mutated genes in the HR pathway, was significantly associated with PDL1-H ( P = 0.01). Conclusions: Our data revealed a subset of patients with ESCC harbored DDR gene mutations. Patients with these DDR gene mutations are significantly associated with immune biomarkers, implying the potential feasibility of combining DDR agents with immunotherapy in patients with DDR deficiency.
Efficacy and safety of second-line regorafenib after sorafenib or lenvatinib first line in patients with unresectable hepatocellular carcinoma: A real-world study.
Authors: Xue Feng , Zhai Jian , Liu Jianwei , Fu Zhigang , Sun Yanfu , Ge Ruiliang , Bai Shilei , Li Xiaowei , Wang Kui , Qu Zengqiang 
Published: June 2022

e16125 Background: To explore the safety, efficacy and long-term prognosis of patients with unresectable hepatocellular carcinoma (HCC) treated with regorafenib after failure of first-line treatment. Methods: This retrospective single center study included 50 unresectable HCC patients who received regorafenib as a second line treatment in our hospital. Based on the difference of first-line targeted drugs, the 50 patients were divided into sorafenib group (n = 22) and lenvatinib group (n = 28). The adverse events, efficacy and long-term prognosis of sorafenib or lenvatinib followed by regorafenib were analyzed. Results: The median age of the 50 patients was 54.5 years. The patients had the following clinical characteristics: ECOG score 0-1, HbsAg positive, cirrhosis, BCLC stage B/C in 95.5%, 95.5%, 90.9% and 90.9% of all patients respectively. The baseline clinical characteristics between the sorafenib and lenvatinib groups were not statistically different (all p > 0.05), except for age and total bilirubin which were in favour of lenvatinib group. Regorafenib was administered oral 160 mg once daily during weeks 1–3 of each 4-week cycle. For 50 HCC patients, the incidence rate of adverse events after accepting regorafenib was 68%. The incidence rate of grade I/II and III/IV adverse events was 60% and 24%, respectively. According to the standards of RECIST 1.1 and mRSCIST, objective response rate (ORR) and disease control rate (DCR) after receiving regorafenib were 14.0%, 62.0% and 22.0%, 60.0%, respectively. There was no significant difference in incidence of all adverse events and grade III/IV adverse events, ORR and DCR between the two groups ( p > 0.05). In terms of long-term prognosis, total overall survival (TOS) and regorafenib overall survival (ROS) in sorafenib group and lenvatinib group were 23.0 months (95% confidence interval [CI]: 15.1-30.9) vs. 29.7 months (95CI: 21.4-38.1), and 11.7 months (95CI: 7.1-16.3) vs. 15.9 months (95CI: 8.3-23.5). The difference was statistically significant ( p= 0.041 and P = 0.045). The regorafenib progression-free survival (RPFS) was 5.6 months (95CI: 1.9-9.2) vs. 8.0 months (95CI: 5.1-10.9) in sorafenib group and lenvatinib group, respectively. The difference was not statistically significant ( P = 0.380). Conclusions: The data suggest that regorafenib is an effective drug for second-line treatment of HCC, with an acceptable toxicity level, an ORR of 14%-22% and a DCR of 62%-60%. Both TOS and ROS in lenvatinib group are better than those in sorafenib group. The possible mechanisms was that EGFR activation limits the response of HCC cells to lenvatinib. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after the disease progresses.