bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of immune checkpoint inhibitor (ICI) related diarrhea/colitis (IMDC) in cancer patients with superimposed GI infections.
Authors: Ma Weijie , Abu-Sbeih Hamzah , Peng Yuanzun , Okhuysen Pablo , Wang Yinghong 
Published: May 2020

e15166 Background: ICI therapies have revolutionized the landscape of cancer treatment. However, their increased use has also contributed to adverse events, e.g. IMDC. Clinically it is difficult to distinguish between infectious etiology or IMDC. It is unclear whether antimicrobial treatment substantially impacts the disease course. Here, we evaluated the characteristics and outcome of IMDC in cancer patients with superimposed diarrheagenic GI infections. Methods: We retrospectively evaluated cancer patients who received ICI with clinical symptoms of IMDC and confirmed stool microbiology of E. coli or non-CMV viral infections either at the time of IMDC, or within 60 days after IMDC diagnosis at MD Anderson Cancer Center 01/2011-08/2019. We described the disease course and outcome of IMDC based on their status of GI infection and antimicrobial treatment. Results: Total 72 patients were included, among them, 50 control patients with IMDC and no GI infection, 22 had diarrheagenic infections, composed of 17 E coli pathogens: Enteropathogenic, Enterotoxigenic, Enteroaggregative, and E coli 0157:H7 serotype; and 5 viral etiologies: Adenovirus, Norovirus, and Sapovirus. Patients in the infection group had higher grade of colitis (42.9% vs 18.4%, P = 0.041), and more frequent hospitalization (86.4% vs 62%, P = 0.052). 68.2% patients in the infection group received infliximab/vedolizumab add-on treatment compared to 40% in the no infection group (P = 0.078). Patients with GI infection and antimicrobial treatment had much higher IMDC recurrence rate than no antimicrobial treatment (50% vs 0, P = 0.015). GI infection was not associated with higher IMDC recurrence or worse overall survival of these patients. Conclusions: IMDC can occasionally be complicated by infection from common GI pathogens. Antimicrobial treatment was mostly used in severe IMDC cases and did not circumvent the need for immunosuppressant or improve the clinical outcomes. GI infection was not associated with higher IMDC recurrence or worse overall survival of these patients. [Table: see text]
Comparative study between image-guided percutaneous biopsies and matched surgical specimens for the evaluation of PD-L1 status in non-small cell lung cancer.
Authors: Zhao Liang , Chen Haojun , Fu Kaili , Zhuang Yanzhen , Lin Qin 
Published: May 2020

e15168 Background: Programmed death-ligand 1 (PD-L1) expression status is a crucial index for identifying patients who will benefit from anti-programmed cell death protein 1 (PD-1)/PD-L1 therapy for non-small cell lung cancer (NSCLC). However, the concordance of Tumor Proportion Score (TPS)between biopsies and matched surgical specimens remains controversial. This study aimed to evaluate the concordance of PD-L1 expression between image-guided percutaneous biopsies and matched surgical specimens. Methods: We evaluated 157 patients diagnosed with operable NSCLC on both surgical tissue sections and matched lung biopsies. The patients underwent either regular computed tomography (CT)-guided biopsy (n = 82) or positron emission tomography (PET)/CT-guided biopsy (n = 75). The concordance between surgical specimens and lung biopsies for PD-L1 TPS was evaluated using Cohen’s kappa (κ) coefficient. Results: Immunohistochemical expression of PD-L1 was evaluated in both surgical resected specimens and matched biopsies in the eligible 138 patients. The concordance rate of PD-L1 expression between surgical tissue sections and matched biopsies was fairly high at 83.3% (115/138), and the κ value was 0.73 (95% CI: 0.63–0.83, P < 0.001). The concordance rate was higher for tissue sections from PET/CT-guided biopsy than for tissue sections from CT-guided biopsy (88.6% [62/70, κ value: 0.81] vs 77.9% [53/68, κ value: 0.66]). Conclusions: PD-L1 TPS was strongly concordant between surgical specimens and matched lung biopsies. Thus, routine evaluation of PD-L1 expression in diagnostic percutaneous biopsies could be reliable for identifying patients who will benefit from anti-PD-1/PD-L1 immunotherapy. [Table: see text]
Association of immune-related adverse effects and survival in responders treated with immune checkpoint inhibitors.
Authors: Kapoor Akhil , Noronha Vanita , Patil Vijay Maruti , Joshi Amit , Menon Nandini Sharrel , Prabhash Kumar 
Published: May 2020

e15172 Background: The development of immune-related adverse effects (irAEs) can corroborate with the response to immune checkpoint inhibitors (ICIs). However, there is very limited data on the association of irAEs with survival in patients who have shown response to ICIs. Methods: This study is a retrospective audit of prospectively collected database of patients who received ICIs for advanced solid tumors. Responders were defined as patients who attained best response of either complete response (CR) or partial response (PR). Time-to-event analysis was done using Kaplan-Meier estimator and hazard ratio was calculated by using Cox proportional model. Results: A total of 155 patients who received ICI during the specified period were evaluated for this study. The response rate was 19.4%. One year OS for responders was 75.6% (SD 8.8) versus 26.1% (SD 5.1). The median OS for patients who developed irAE was 12.3 months (95% CI: 8.9-15.6) while it was not reached for patients without irAE (HR 10.5, 95% CI 1.2-NR, p=0.007). One-year OS for the corresponding group of patients was 53.6% (SD 15.6) versus 92.9% (SD 6.9), respectively. Conclusions: This study reports negative association of immune-related adverse effects and survival in responding patients of solid tumors treated with immune checkpoint inhibitors. [Table: see text]
Analysis of microsatellite instability differences in eight types of tumors.
Authors: Zhang Zhen , Zhang Xing , Ge Minhui , Qin Huijuan 
Published: May 2020

e15174 Background: Microsatellite instability-high (MSI-H) is the gain or loss of nucleotides from repetitive DNA caused by genomic hypermutability and a powerfully predictive phenotype for diagnosis, immunotherapy and prognosis in various types of cancer. Herein, we analyze the frequency of MSI-H for the understanding of epidemiology of MSI-H across major types of human cancer. Methods: MSI value was calculated by bioinformatics algorithm based on NGS from 539 genes panel in tumor tissue. Patients were divided into three classes as MSI-H, MSI-L and MSS based on MSI value. MSI-H was defined as above 10% positive of the 195 tested microsatellites sites, and this method was totally consistent with conventional MSI-PCR testing in research and development sample verification. We compared the differences of MSI-H ratio in eight types of human cancer including liver cancer, bile duct cancer, gastric cancer, colorectal cancer, pancreatic cancer, melanoma, glioma and lung cancer from 874 cancer cases via χ2 test, adjusted standardized residual or Fisher's exact test. Results: The ratios of MSI-H in eight types of solid tumors were 0% in 32 patients with bile duct cancer or 27 patients with pancreatic cancer, 0.6% (1/174) in liver cancer, 1.9% (1/54) in gastric cancer, 6.7% (8/119) in colorectal cancer, 3.1% (1/32) in melanoma, 4% (1/25) in glioma, and 0.5% (2/411) in lung cancer, respectively. Significant correlations between the MSI-H and cancer types were found by χ2 test (χ2 = 26.571, Cramer’s V coefficient = 0.174, p = 3.980×10−4). Only patients with colorectal cancer had absolute values of adjusted standardized residual above 3, its observed counts of MSI-H significantly higher than expected counts. Fisher’s exact test was performed to analyze the differences of MSI-H ratio across hepatobiliary (liver and bile duct) cancer, digestive tract (gastric and colorectal) cancer and lung cancer, and we found the MSI-H ratio of patients with digestive duct cancer was significantly higher than patients with hepatobiliary cancer ( p = 0.007) or lung cancer ( p = 4.599×10−4). Conclusions: Our study provided new references to cancer-specific properties and clinical diagnosis of MSI especially in East Asian populations. As a retrospective study with a relatively small population, the conclusions of this study needed to be verified with a larger sample.
Monitoring of inflammatory response to cancer immunotherapies.
Authors: Quan Qimin , Geanacopoulos John , Ritchey Joshua , Clenow Mark , Wilkinson Joe , Boyce John 
Published: May 2020

e15199 Background: Inflammation observed in response to some monoclonal antibody drugs and adaptive T-Cell therapies has become a major issue in cancer immunotherapy. Prognostic monitoring of the inflammatory response requires simultaneous measurement of multiple cytokines at widely divergent concentrations. At present, no analytical method, known to us, can provide large dynamic range (> 6 logs), high sensitivity (< 1pg/ml) and high multiplex in a single test. Methods: The NanoMosaic platform is a cytokine quantification technology powered by silicon nanoneedle biosensors that are densely integrated on a plate and manufactured with CMOS-compatible nanofabrication processes. Each nanoneedle is a label-free biosensor, functionalized with capture antibodies. Each analyte specific sensing area consists a total of ~23k nanoneedles divided into a digital region (~20k nanoneedles) and an analog region (~3k nanoneedles), combined to cover the entire range of inflammatory biomarkers from 0.1pg/ml to 1ug/ml. Results: We demonstrated that the digital nanoneedles achieve the single molecule sensitivity. Therefore, at ultra-low concentrations when antigens that are captured by the nanoneedles follow Poisson statistics, the number of antigens can be quantitated by counting the presence or absence of color changes of individual nanoneedles in a binary fashion. As the protein concentrations increase, the binding events increase accordingly and achieve saturation when all nanoneedles capture more than one protein. Above the digital saturation concentration, an adjacent section of analog nanoneedles perform quantitative analysis based on the level of color change, thus providing a wider dynamic range up to 1ug/ml. Each single analyte area, including both digital and analog sensors, is less than 500um. Therefore, high level multiplex can be achieved by duplicating the detection sensor in a microarray format without loss of sensitivity and dynamic range. Conclusions: The CMOS-compatible NanoMosaic technology provides the cost-effectiveness, sensitivity, dynamic range and multiplexing capacity required to fully integrate patient immune response into therapeutic development and decision making.
Generation of dendritic cells using viral lysate of tumor cells in vitro.
Authors: Kolpakov Sergey A. , Kolpakova Elena P. , Sitkovskaya Anastasia O. , Zlatnik Elena Yu. , Filippova Svetlana Yu. , Bondarenko Elena S. , Kolesnikov Vladimir E. , Oganyan Nairi B. , Pavlov Vladislav K. , Karasev Timofey S. , Kit Oleg I. 
Published: May 2020

e15202 Background: The purpose of the study was to investigate the effect of a new unclassified rotavirus on the effectiveness of maturation of dendritic cells (DC) and their activation of lymphocytes in vitro. Methods: Strain No.100 of the RVK virus was isolated by S.A. Kolpakov and characterized as rotavirus. U87MG cell lysate (glioblastoma) was obtained by incubation with 108 RVK particles in the DMEM medium with L-glutamine for 72 hours; a cytopathic effect was observed. Immature DCs were cultured for 7 days in the presence of IL-4 and GM-CSF. For antigen loading of DCs, we used the following options for 48 h: a) U87MG lysate obtained by repeated freeze-thaw cycles (TL); b) U87MG lysate obtained by co-cultivation with RVK (VTL); c) RVK. To assess the DC ability to activate autologous lymphocytes, they were co-cultured for 5 days in a 3:1 ratio. Results: The use of VTL culture for DC loading caused an increase in the expression of mature DC (mDC) markers compared to TL: the number of CD83+/CD86+ cells increased by more than 2 times, CD83+/CD80+ by 1.2 times, CD83+HLA-DR - by 5.5 times. With VTL, expression of markers of immature DCs (CD1a, CD14) was minimal. The use of RVK as an antigen induced the generation of DCs from monocytes, but their maturation was much less pronounced: a significant increase in the membrane expression of CD86, but not CD83, was determined. These DCs demonstrated a higher expression of markers of immature DCs, compared to stimulation with cell lysates (both TL and VTL): CD1a and CD14; CD80+/CD86+ level was the highest among all options. Analysis of the DC effect on co-cultivated lymphocytes showed that DCs loaded with RVK, both alone and as part of VTL, stimulated predominantly the NKT subpopulation. The same samples contained more T lymphocytes, activated CD4+ and CD8+ compared to samples stimulated by TL. However, the samples co-cultivated with VTL contained the maximal amount of CD4+/CD25+/CD127dim phenotypically corresponding to Tregs. Conclusions: The antigen loading of immature DCs with RVK alone causes their activation, but not maturation, which is not realized in typical terms of the DC generation from blood monocytes. The presence of RVK, including in VTL, has a stimulating effect on NKT lymphocytes suggesting the possible generation of specific highly active cytotoxic lymphocytes.
Use of alpelisib in the treatment of hormone receptor positive metastatic breast cancer: An institutional experience.
Authors: Lama Tamang Tsering G. , Kyung Daniel , Eisenbud Lauren , Tang Tianyi , Parajuli Ritesh , Mehta Rita S. 
Published: May 2020

e15216 Background: Mutations in PI3K pathway is a known mechanism of resistance to endocrine therapy in breast cancer. Alpelisib is an alpha-specific PI3K inhibitor. Alpelisib with Fulvestrant is approved for treatment (Tx) of PIK3CA mutated HR+ metastatic breast cancer (MBC) that progress on hormonal therapy. Despite its approval by the FDA, real world data on the use of Alpelisib for the management of MBC is lacking. This abstract reviews the safety and efficacy of Alpelisib in the management of patients with MBC. Methods: A retrospective review of the tumor registry database at a single institution was conducted to identify patients with HR+ MBC. Detailed clinical and pathologic data of PIK3CA mutated patients treated with Alpelisib were obtained. Genomic profiling was done with Foundation One. Results: Table highlights the characteristics of the four patients. All were treated with Alpelisib and Fulvestrant after PIK3CA mutation was demonstrated. 3 patients were heavily pretreated with systemic Tx including CDK 4/6 inhibitors. All patients responded to Alpelisib and Fulvestrant despite treatment history. Mucositis, rash, hyperglycemia and pancytopenia were the observed adverse events (A/E). All A/E were adequately managed except in one patient that required discontinuation of Tx. None has clinically progressed. Conclusions: Our data suggests that Alpelisib and Fulvestrant is tolerated and improves outcomes in patients with HR+ MBC. Alpelisib and Fulvestrant could be an effective therapy in patients who have also progressed on systemic chemotherapy including CDK 4/6 inhibitors. Although our sample size is small, we hope that our experience could guide clinicians in the management of patients with HR+ MBC who harbor the PIK3CA mutation and are being treated with Alpelisib. [Table: see text]
PIK3 mutation as a predictor of immune checkpoint inhibitor response.
Authors: Jacob Aasems , Wu Jianrong , Chauhan Aman 
Published: May 2020

e15257 Background: Although several biomarkers predicting response to immune checkpoint inhibitor (ICI) therapy have been evaluated, the emerging data is conflicting. There is a lack of real-world data that might help identify biomarkers in diverse populations. Methods: Patients with solid tumors who received ICI and underwent tumor tissue next generation sequencing (NGS) in our institution between 2016-2019 were included in the study. Response to ICI was assessed based on RECIST 1.1 and median progression free survival (mPFS), radiologic response and immune-related adverse events (IRAEs) were analyzed in relation to various molecular biomarkers. Results: 69 patients had complete NGS and RECIST 1.1 data required for analysis. Study cohort included 14 different cancer types. 78% of the patients were smokers. TP53 (62%), CDKN2A (44%), NOTCH1/2 and PIK3 (33%) were the most common mutations identified. 42% patients had CR/PR with ICI and mPFS was 38 weeks (w). A statistically significant improvement in PFS was observed in patients with PIK3 mutated cancers (mPFS 123 weeks vs. 23 weeks, p = 0.012). These patients also had a higher percentage of response (60.9% vs 39.1%, p = 0.5), and were also associated with increased risk of immune related adverse events (IRAEs) (73.9% vs. 37%, p = 0.004). PIK3 mutation had no association with PDL1 status or tumor mutational burden (TMB). Mean TMB was 12.59, and 29% patients had positive PDL1 expression. There was significant difference in mPFS between high (≥20mut/Mb) and low/intermediate TMB (0-19mut/Mb) (mPFS 18w vs. 65 w, p = 0.049) as well as PDL1 positive and negative tumors (40w vs. 18w, p = 0.059). BRAF mutation was associated with early progression in all cancers (mPFS 17w vs 39w, p = 0.033). Conclusions: Conventionally, a marker of poor survival and chemotherapy response, PIK3 mutation was associated with positive ICI response in our study. High incidence of IRAEs in PIK3 mutants also point towards increased ICI activity. High TMB, as expected was associated with ICI response.
T-cell inflamed gene expression to predict prognosis and response to immune checkpoint inhibitors.
Authors: Yu Yao , Ma Jingjiao , Chen Jie , He Ning , Xu Xiaohong , Wang Lingyu , Lin Rongbo 
Published: May 2020

e15264 Background: To prove that T-cell-inflamed gene-expression profile (GEP) can predict prognosis and response to immune checkpoint inhibitors (ICIs) in the real-world study. Methods: 36 patients admitted from January 2018 to December 2018 were enrolled, including 15 patients with advanced NSCLC, 12 with advanced bladder cancer and 9 with advanced liver cancer. All patients were treated with nivolumab or pembrolizumab and provided informed written consent for analysis. Tumor total RNA was isolated from pretreatment FFPE samples and RNA-seq was performed on the Illumina NovaSeq 6000 system. GEP was calculated as a weighted sum of normalized expression values for 18 genes, as described in the article written by Ayer M, et al. in 2017. The data cutoff date was July 30, 2019. Primary end points were objective response rate (ORR) and disease control rate (DCR). Secondary end point was progression-free survival (PFS) assessed per RECIST v1.1. 95% CIs and P values for ORR and DCR were evaluated by the binomial exact method. Correlation between GEP and ORR, DCR and PFS was assessed by Wilcoxon rank sum test and Cox regression model, respectively. Survival curves were estimated by Kaplan-Meier methods. Cut-off value of GEP was confirmed by the Youden Index. The comparisons of DCR and PFS were performed by Fisher’s exact test and log-rank test, respectively. Results: ORR was 30.6% (95% CI, 16.3%-48.1%) and DCR was 50.0% (95% CI, 32.9%-67.1%). Median PFS was 3.9 months (95% CI, 0.8-NR). We found that GEP was higher in patients who achieved DCR and had longer PFS. And then GEP was significantly associated with DCR (p = 0.019) and PFS (p = 0.005), but not significantly with ORR (p = 0.42). Based on Youden Index, cut-off value of GEP was confirmed as -0.368, with 94.4% of sensitivity and 66.7% of specificity. According to cut-off value, 23 patients were evaluated as GEP-H. GEP-H group had higher DCR and longer PFS (DCR: 73.9% vs 7.69%, p = 0.0003; mPFS: 7.0m vs 2.1m, p = 0.00049). Conclusions: GEP can predict prognosis and response to ICIs in multiple cancers in our real-world study. Interpretation of these data may be limited by small sample sizes. Further studies are being conducted.
An open-label phase Ib study to determine safety and preliminary efficacy of oral Lucitanib (AL3810) in patients with locally advanced or metastatic gastric, hepatocellular, nasopharyngeal carcinoma, malignant biliary, and thymic tumors.
Authors: Pan Hongming , Qin Shukui , Zhang Li , Li Jin , Xu Jianming , Xu Ruihua 
Published: May 2020

e15502 Background: Angiogenesis is an essential prerequisite for tumor growth, invasion and metastasis. Targeting tumor angiogenesis has become a common therapeutic target in clinical work. Lucitanib, an oral tyrosine kinase inhibitor, precisely targets FGFR/VEGFR/PDFGR. In this study, we evaluated the safety profile and preliminary anti-tumor effects of lucitanib in patients with locally advanced or metastatic gastric (GC), hepatocellular (HCC), nasopharyngeal carcinoma (NPC), malignant biliary (MBT) and thymic tumors (TT). Methods: Patients (Pts) with locally advanced or metastatic GC, HCC, NPC, BTC and TT, standard therapy failed, ECOG status ≤1, were enrolled. Total 44 subjects (6 GC, 4 HCC, 10 BTC, 4 TT, 20 NPC) were recruited, then randomized into two groups with lucitanib 10 mg QD given continuously (CON) or intermittently (INT) lucitanib 10 mg QD three weeks on and one week off. Results: 22 pts were included in CON and INT group respectively. The most common drug-related treatment emergent adverse events (TEAEs) for CON (AE≥10%, Grade≥3 ): proteinuria (19 [86.4%], 4 [18.2%]), hypertension (18 [81.8%], 7 [31.8%]), haematuria (3 [13.6%], 0), aspartate aminotransferase increased (8 [36.4%], 1 [4.5%]), hypothyroidism (7 [31.8%], 0), blood creatinine increased (5 [22.7%], 0), platelet count decreased (5 [22.7%], 1[4.5%]), white blood cell count decreased (3 [13.6%], 0), weight decreased (4 [18.2%], 0), diarrhea (4 [18.2%], 0) and rash(6 [27.3%], 0). For INT: proteinuria (8 [36.4%], 1[4.5%]), hypertension (9 [40.9%], 4 [18.2%]), hypothyroidism (6 [27.3%], 0), platelet count decreased (3 [13.6%], 0), white blood cell count decreased (4 [18.2%], 0). Treatment discontinuation due to drug-related TEAEs were 3 pts (13.6%) and 1 pt (4.5%) in CON and INT respectively. Preliminary efficacy for CON: ORR: 13.6%, DCR: 72.7%, median PFS: 3.8 months; for INT: ORR: 4.5%, DCR: 40.9%, median PFS: 1.9 months. Conclusions: Although CON exhibited higher incidence, drug-related TEAEs at both groups were expected and manageable. Lucitanib exhibited better efficacy profile when administrated 10mg QD continuously. Further safety and efficacy of lucitanib is being evaluated in phase II/III studies. Clinical trial information: 03260179.