bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in neutrophil /lymphocyte ratio and platelet count after chemotherapy correlate with cheomtherapy response and predicition of prognosis in patients with advanced gastric cancer.
Authors: Liu Yibing , Meng Qingju , Zhou Zhiguo , Jing Li 
Published: June 2021

e16030 Background: The aim of the study was to investigate the predictive value of neutrophil to lymphocyte ratio(NLR) and platelet count(PLT) in the prediction of chemotherapy response and prognosis in patients with advanced gastric cancer. Methods: In this retrospective study, a total of 260 advanced gastric cancer patients were analyzed and the correlation between NLR, PLT and overall survival (OS) were investigated. The receiver operating curve (ROC) was drawn to determine the optimal critical value of NLR. These cases were included and separated into different groups according to the median values of NLR or PLT. Results: Low baseline NLR level correlated with improved clinicopathological characteristics, including organ-free metastasis, Borramn type I and II, tubular adenocarcinoma and papillary carcinoma. Low baseline PLT level also associated with Borramn classification. Alterations in the NLR and PLT levels were associated with therapeutic efficacy and prognosis. The patients who remained in or switched to the low NLR level had an improved objective response rate(ORR), disease control rate(DCR) and survival ratios. The patients who remained in or switched to the low PLT level had an improved DCR. Univariate analyses showed that pathological type, Borramn typing, changes of NLR, and efficacy of chemotherapy were significant predictors of OS. Multivariate analyses showed that pathological type and efficacy evaluation were independent prognostic factor. Conclusions: This study demonstrated that the changes of NLR and PLT following chemotherapy can predict the chemotherapy results in patients with advanced gastric cancer. But, baseline NLR and PLT level haven’t prognostic value in patients with advanced gastric cancer. However, pathological types and the results of the first therapeutic evaluation could have prognostic value in patients with advanced gastric cancer.
Effects of Qingre Huatan Huoxue prescription on biological characteristics and cell cycle proteins of esophageal cancer stem cells.
Authors: Si Fuchun 
Published: June 2021

e16052 Background: Esophageal cancer (EC) stem cells characterized with immature differentiation, high invasion, high tumorigenesis and other biological characteristics, which are the root of the occurrence, development, recurrence, metastasis of EC. In this study, its purpose is to select and identify EC stem cells from serum-free cultured EC9706 cells, explore the effect of Chinese herbal prescription and its separated prescriptions on the biological characteristics of EC9706 stem cells, and to reveal the cytological and molecular mechanisms of Chinese herbal prescription anti-cancer. Methods: Firstly, MTT method was applied to explore the serum-free culture conditions of EC9706 stem cells in diameter of 60 mm low adhesion culture dish, at the same time, applying flow cytometry to identify the p75NTR mark ratio of each passage of cell to screenEC9706 stem cells. Next, Plotting the growth curve of EC9706 stem cells, detecting the proliferation inhibition rate EC9706 stem cells by cisplatin, soft agar clone formation, cell cycle to identify the characteristics of EC9706 stem cells by MTT method, soft agar assay, flow cytometry. Then applying MTT method and orthogonal test to screen and optimize Qingre Huatan Huoxue prescription (QHHP), using flow cytometry and western blot to test the effects of QHHP and its separated prescriptions on EC9706 stem cells appraisal indicators and Cell Cycle Proteins. Results: EC9706 cells with concentration of 8×104 cells/dish inoculateed on diameter of 60mm low adhesion culture dish, with adding 5 ml DMEM/F12 medium, a daily supplement of 20ng EGF, 10ng bFGF, per 10 to 14 days to passage one generation. After 5 generations of cell passage, the expression rate of p75NTR was 4-5%, was selected as the experimental object.EC9706 stem cells with the biological characteristics of slower adhesive growth, stronger cisplatin resistance, higher soft agar clone formation and p75NTR expression rate than that of EC9706 cells, and The cell cycle distribution was concentrated in the G0/G1 phase. 6 Chinese herbs were screened out ( Coptis coptidis, Rhizoma officinalis, Cucurbita pedicle, Toona bark, Cantharidopsis cantharidis, Augustia japonica) and compose QHHP. QHHP and its separated prescriptions could change the morphology, colony formation ability and cycle distribution of EC9706 stem cells in serum-free culture condition, which were related to the BMI1/CyclinB1 signaling pathway. Conclusions: Serum-free cell culture is a method to enrich stem cell-like cells in EC9706 cells. Qingre Huatan Huoxue prescription and its separated prescriptions inhibited the proliferation of EC9706 stem cells and change esophageal cancer stem cells characters. The mechanism of QHHP and its separated prescriptions on stem cells in EC9706 cells was related to BMI1 /CyclinB1 signaling pathway.
Time to review the role of intraluminal brachytherapy for dose escalation after concurrent chemoradiation in cancer esophagus: A retrospective audit.
Authors: Mehta Ankita , Kumar Piyush , Gupta Richa , Garg Ayush , Agarwal Shubhi 
Published: June 2021

e16054 Background: Intraluminal brachytherapy (ILBT) for dose escalation after concurrent chemoradiation (CRT) in cancer esophagus is not routinely practiced. This is particularly attributable to radiotherapy toxicity in terms of strictures and fistulas. Cancer esophagus has poor locoregional control and overall survival rates in comparison to head and neck cancers. Dose escalation may be an option to counteract the high failure rates. Methods: A retrospective analysis was conducted for esophageal cancer patients treated between 2008 to 2016 planned for radical CRT to a minimum dose of 59.4 Gy in 33 fractions along with concurrent cisplatin 35 mg/m2 and 5 FU 375 mg/m2 on weekly basis. Further, the patients who received dose escalation after external beam radiotherapy (EBRT) completion by ILBT to a dose of 6 Gy in a single fraction to the pre EBRT volume were also analysed. The patient, tumor, treatment characteristics along with response rates, survival outcomes, and toxicities were evaluated and compared between the two groups - the patients who received ILBT and those who did not. Statistical significance between variables was analysed with the Chi-Square or Fischer’s exact test and t-test. Survival analysis was done by Log-Rank test. The analysis was done on a worst-case scenario basis where the patients lost to follow-up were considered dead. Results: The total number of patients treated by CRT was 69, out of which 13 patients received ILBT for dose escalation. The median age was 60 years (Range - 40 to 80 years) and the male: female ratio was 1.09, mean tumor length was 6.4 ± 2.4 cms (Range-1.5-12 cms). The commonest tumor site was the middle third observed in 58% patients. The median EBRT dose was 59.4 Gy (Range- 9 to 63 Gy). The median concurrent chemotherapy cycles were 5. The median follow-up period was 15 months (range 1-100 months). In terms of complete response rates, there was a trend towards significant improvement in patients receiving ILBT compared to those receiving EBRT alone (84.61% versus 57.49%, p=0.07). Also, the overall survival (OS) was significantly higher in the ILBT group (45.31 months versus 19.20 months; p = 0.005). The other patient, tumor, and treatment characteristics analyzed showed no significant impact on OS. There was no significant difference in the incidence of strictures (p=0.206) and severity (p=0.764) of strictures amongst both the groups. Grade ≥3 late toxicity was reported in 10 patients (17.85%) receiving EBRT alone and in 3 patients (23.07%) receiving ILBT. None of the patients receiving ILBT developed a fistula. Conclusions: The present study reveals a dramatic increase in OS by dose escalation with ILBT. The limitations of the present study were a small sample size and a lesser number of patients in the ILBT group. Recapitulating the concept of ILBT to increase the local tumoricidal dose may improve the survival rates.
Predictors of clinical outcomes in patients undergoing curative treatment for esophageal or gastroesophageal junction adenocarcinoma.
Authors: Magge Tara , Van Haren Robert , Starnes Sandra Lynne , Wilson Gregory , Patel Sameer H. , Kharofa Jordan , Sohal Davendra 
Published: June 2021

e16067 Background: Management of locally advanced esophageal and gastroesophageal junction (E/GEJ) adenocarcinoma is typically managed with neoadjuvant treatment followed by surgery. Clinical outcomes remain suboptimal and a considerable proportion of patients develop recurrence. However, prognostic and predictive factors are not well-defined. We thus aimed to identify any factors that were associated with disease recurrence and decreased overall survival (OS) among patients with E/GEJ adenocarcinoma treated with curative intent. Methods: A retrospective study spanning 2011-2020 was performed, which identified 56 patients who underwent esophagectomy for E/GEJ adenocarcinoma at the University of Cincinnati. Data on baseline demographic and clinical characteristics, treatment details, pathologic outcomes, recurrence patterns, and survival were extracted from the electronic medical record. Predictors of recurrence and OS, using multivariable logistic regression and Cox proportional hazards analyses, respectively, were identified using all potential predictors and parsimonious modeling. The study was approved by the UC IRB; statistical analyses were performed using SAS 9.2; 95% confidence intervals and two-sided p-values were calculated. Results: Of the 56 patients included, 50 (89%) were White and 6 (11%) were Black; 46 (82%) were male and 48 (85%) were current or former smokers. Tumor location was E in 37 (66%) and GEJ in 19 (34%) patients; 30 (64%) had cT3 or cT4 tumors and 27 (55%) had node-positive disease. Neoadjuvant treatment included platinum-based chemotherapy for 43 (77%) and radiation for 40 (71%) patients; all patients underwent esophagectomy. Median OS for the entire cohort was 4.2 (95% CI 1.8-NR) years and 23(41%) had recurrence after resection. Multivariable modeling showed body mass index (BMI) < 25 (OR vs. BMI ≥ 25: 5.41, 95% CI 1.4-20.4, p = 0.01) to be associated with recurrence; a higher pathologic T stage showed a trend toward increased risk (pT stages 1, 2, and 3 patients (vs. pT 0) were 0.2, 1.1, and 2.5 times more likely to have recurrent disease, respectively. OS was inferior for patients with recurrence (HR for death, vs. no recurrence: 5.42, 95% CI 2.1-13.8, p < 0.001) and a baseline ECOG PS ≥2 (HR vs. ECOG PS < 2: 2.36, 95% CI 0.87-6.4, p = 0.09). Conclusions: In this dataset of patients with E/GEJ adenocarcinoma treated with curative-intent resection, baseline clinical parameters of lower BMI and worse ECOG PS (rather than disease characteristics such as T and N stage) were the main predictors of recurrence and decreased OS. These findings suggest that improving clinical outcomes may at least partly depend on prehabilitation targeting nutrition and physical therapy for patients undergoing curative treatment for E/GEJ adenocarcinoma.
Development and validation of a nomogram for distant metastasis in esophageal cancer based on radiomics and clinical factors.
Authors: Chao Zhu , Qiu Qingtao , Ji Youxin , Wang Songping , Ding Jialin , Wang Linlin 
Published: June 2021

e16071 Background: Distant metastasis with an incidence of 25% in esophageal cancer(EC) represents a poor prognosis. However, there was few study for prediction of distant metastasis in EC, due to unsatisfactory specificity of clinical factors and lack of reliable biomarkers. Methods: Two hundred and ninety-nine patients were enrolled and randomly assigned to a training cohort(n = 207) and a validation cohort(n = 92). Logistic univariate and multivariate regression analyses were used to identify clinical independent predictive factors and construct a clinical nomogram. Radiomic features were extracted from contrast-enhanced CT performed before treatment, and Lasso regression was used to screen the optimal features, which were developed a radiomics signature subsequently. Four machine learning algorithms were used to establish radiomics models respectively based on the screened features. The joint nomogram incorporating radiomics signature and clinical independent predictors was developed by logical regression algorithm. All models were further validated by discrimination,caliberation, reclassification and clinical usefulness. Results: The joint nomogram had a better performance [AUC(95%CI): 0.827(0.742-0.912)] than clinical nomogram [AUC(95%CI): 0.731(0.626-0.836)]and radiomics predictive models[AUC(95%CI): 0.747(0.642-0.851),SVM algorithms]. Caliberation curve, and decision curve analysis also revealed joint nomogram outperformed the other models. Compared with the clinical nomogram, net reclassification Improvement(NRI) of the joint nomogram was improved by 0.114(0.075, 0.345),and integrated discrimination Improvement (IDI) was improved by 0.071(0.030-0.112), P= 0.001. Conclusions: We constructed and validated the first joint nomogram for distant metastasis in EC based on radiomics signature and clinical independent predictive factors, which could help clinicians to identify patients with high risk of distant metastasis.
Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and hemoglobin (Hb) predict immunotherapy outcomes in patients with advanced or metastatic gastric cancer.
Authors: Gou Miaomiao , Zhang Yong , Yan Huan , Si Haiyan , Wang Zhikuan , Dai Guanghai 
Published: June 2021

e16075 Background: This study aimed to confirm the prognostic role of pretreatment neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), hemoglobin (Hb) levels as effective and convenient biomarkers for patients with advanced or metastatic gastric cancer (AGC or MGC) receiving immunotherapy. Methods: patients with AGC and MGC who received anti-PD-1 treatment at the Chinese PLA General Hospital between January 2016 and November 2020 were reviewed. The receiver operating characteristic analyses for predicting 6 months PFS by the NLR, PLR was used to identify an appropriate cut-off value. The study analyzed the association of NLR, PLR, Hb and overall survival (OS) or progression-free survival (PFS) and anti-tumor response rate with immunotherapy respectively. Results: 137 patients were included in the final analysis. 71 patients were administered immunotherapy in the first line and the rest of the patients in the second or further line. 92 patients had received immunotherapy combined with chemotherapy, whereas 45 patients had undertaken immunotherapy monotherapy or with anti-angiogenesis. The best cut-off value for NLR was 3.23 and for PLR was 816.43. NLR <3.23 was associated with longer OS (HR = 0.38, 95% CI, 0.26-0.57, p < 0.001) and PFS (HR = 0.42, 95% CI, 0.29-0.62, p < 0.001) in patients with AGC or MGC. Patients in PLR<816.43 group had prolonged PFS (7.9m vs 4.3m, p<0.001) and OS (11.1m vs9.2m, p<0.001) than in PLR>=816.43 group. The median PFS was 7.8m in the normal Hb level group (Hb>=110g/L) and 4.3m in the decreased Hb group (Hb<110g/L) (HR=0.5, 95% CI 0.31, 0.81, P=0.004). The OS was 14.4m with normal Hb level as compared with 8.2m with decreased Hb level( HR=0.59, 95% CI 0.37, 0.94, P=0.024). No significant difference was observed in objective response rate (ORR) and disease control rate (DCR) in the different NLR, PLR, Hb group, respectively. Univariate and multivariate analysis found that NLR, PLR, Hb were independent prognostic biomarkers for PFS and OS (p<0.05). Conclusions: pre-treatment NLR, PLR, Hb was significantly associated with PFS and OS in patients with AGC and MGC who received immunotherapy. Clinicians need to consider patients with elevated NLR and PLR or decreased Hb level for decisions on immunotherapy strategy.
Integrated DNA and RNA sequencing to reveal early drivers of metastasis in gastric cancer.
Authors: Zhang Jieyun , Liu Fatao , Yang Ya'nan , Weng Xiaoling , Yang Yue , Gong Zhe , Huang Shenglin , Gan Lu , Zhang Xiaowei , Gong Yiwei , Liu Yun , Guo Weijian 
Published: June 2021

e16096 Background: Gastric cancer (GC) is the second cause of cancer-related death and metastasis is an important cause of death. Considering difficulties in searching for metastatic driver mutations, we tried a novel strategy to identify early drivers in primary gastric tumors. In this study, we conducted an integrative genomic analysis on GC patients and identified early drivers that lead to metastases. Methods: Tumors and matched normal tissues from 400 Chinese GC patients were characterized by whole-exome sequencing (WES), transcriptome sequencing and targeted exome sequencing (TES), especially the comparative analysis results between higher metastatic potential (HMP) group with T1 stage and lymph-node metastases, and lower metastatic potential (LMP) group without lymph-nodes or distant metastases. Functional experiments on candidate driver mutations were applied in GC cell lines to explore their roles in metastasis and immune escape. Results: HMP group presented higher mutation load and heterogeneity, enrichment in immunosuppressive signaling, lower tumor purity, more stromal and immune cell infiltration than LMP group. We identified 262 differentially expressed mRNA, lncRNA and miRNA between HMP and LMP group (with more than twice proportion of 2-fold increased or decreased tumor than normal tissue in HMP than LMP group, and with significantly 2-fold higher or lower in HMP tumors than LMP tumors). 168 candidate prometastatic mutations were found by WES and 8 were selected for following TES to detect their association with distant metastasis. We found that four candidate mutations were related to distant metastasis and mutated TP53 and MADCAM1 were significantly associated with poor metastasis-free survival. It’s worth noting that though with low mutational rate, MADCAM1 mutations were only observed in patients with metastasis within three years after surgery or at diagnosis. We demonstrated that MADCAM1-mutated proteins act as GOF mutants and could not only directly promote cancer cells migration, but also could trigger tumor metastasis by establishing complicated immunosuppressive microenvironment, including promoting PD-L1-mediated immune escape and reprogramming tumor-associated macrophages (TAMs). Conclusions: Our results showed that the GCs with different metastatic potential are distinguishable at the genetic level. A number of potential metastatic driver mutations was revealed in this study including known cancer-associated genes TP53. We also discovered some novel driver mutations, such as MADCAM1. The results indicate driver mutations in early-onset metastatic GC could promote metastasis not only by directly empower cancer cells to disseminate but also by establishing an immunosuppressive microenvironment. This study increased the understanding of molecular landscape of GC patients and provided possibility for future target therapy.
Pre-treatment status of inflammation-based biomarkers in the patients with advanced gastric cancer who will be treated with nivolumab.
Authors: Kusumoto Tetsuya , Kudou Kensuke , Nanbara Sho , Tsuda Yasuo , Kusumoto Eiji , Hashimoto Kenkichi , Sakaguchi Yoshihisa , Ikejiri Koji , Oki Eiji 
Published: June 2021

e16107 Background: Nivolumab is currently proved to be one of the most recommended regimens as the third-line chemotherapy for patients with advanced gastric cancer (AGC) in Japan. A variety of scores based on the systemic inflammation-based biomarkers have been reported to reflect survival in cancer patients. Kudou et al. recently reported that newly designed combined score of 5 inflammation-based prognostic scores (IBPSs), composed of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, Glasgow prognostic scale, prognostic index and prognostic nutritional index, might be predictive for the prognosis of resected gastric cancer (Ann Surg Oncol, 2020). The aim of the study is to investigate the clinical significance of nivolumab monotherapy in patients with AGC, associated with pre-treatment status of IBPSs including Kudou’s combined score (min 0 to max 10). Methods: Thirty-six patients received nivolumab monotherapy in our institute and enrolled to this retrospective study. We conducted a retrospective review of the data of 24 patients with AGC who received ≧ 2 cycles of nivolumab as the 3rd-line chemotherapy. Adverse events, tumor responses, the IBPSs and survival data were analyzed. Results: Three patients quitted the continuation of nivolumab except for the progressive disease, due to non-hematological toxicities higher than grade 3 including myositis, hypothyroidism, dermatitis and liver dysfunction. The rate of hematological toxicities, which showed severe anemia of higher than grade 3 was 20.8%. The ORR and the DCR were 4.2% and 41.7%, respectively. The median PFS and the OS after nivolumab administration were 69 and 274 days, respectively. Pre-chemotherapeutic combined score of IBPSs below 7 was significantly associated with the longer OS (P=0.014) in exposure of nivolumab, compared with the patients group presenting more than 7. Conclusions: Nivolumab monotherapy as the 3rd-line is one of the best regimens for patients with AGC showing better PS or lower combined score of IBPSs.