bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 514: Specific anti-HER2 host immunity conferred by HER2-targeted antibody drug conjugate therapy and checkpoint blockade
Authors: Qin You , Dobson Hannah E. , Comer Frank I. , Chang Alfred E. , Wicha Max S. , Li Qiao 
Published: July 2021

Abstract
Using HER2-targeted antibody drug conjugates (ADC), we tested the therapeutic efficacy, direct impact on cancer stem cells (CSCs), and potential added benefit when combined with PD-L1 blockade in immunocompetent mouse tumor models. Two murine mammary tumor models were used in this study: D2F2/E2, a cell line resulting from stable transfection of parental D2F2 murine mammary tumor cells with wild-type human HER2, and 4T1-HER2, derived from parental 4T1 by stable transduction with wild-type human HER2. We demonstrate that HER2-targeted ADC treatment induced both cellular and humoral anti-HER2 adaptive immune responses which effectively targeted both bulk tumor and cancer stem cells. We recently investigated induction of host immunity using a tumor re-challenge strategy in tumor free animals subjected to ADC or ADC + anti-PD-L1 therapy. D2F2/E2 tumor-bearing mice were treated with ADC or ADC + anti-PD-L1 to generate tumor free mice. These tumor free animals were re-challenged with the relevant tumor D2F2/E2 or irrelevant tumor WT 4T1 respectively. While all the tumor free animals re-challenged with WT 4T1 showed aggressive tumor growth, ADC-treated tumor free animals re-challenged with D2F2/E2 demonstrated significantly (p&lt;0.0001) slower tumor growth compared with the age-matched naive mice, and this protection was significantly (p=0.0078) enhanced in ADC + anti-PD-L1-treated tumor free animals, resulting in completely rejection of the re-challenge and thus documenting immunological memory formation. B cell activation was obvious by the significant upregulation of Ki67 and GL7 CD86 on both CD45+CD19+ tumor-infiltration lymphocytes (TILs) and splenocytes. B cell differentiation was evident by the upregulation of GL7 on both TILs and splenocytes, as well as the expression of CD138 on splenotytes. We found that IgG1 was the predominant isotype in treated mice vs. IgG2a, IgG2b, IgG3, and ADC + anti-PD-L1 dual treatment drastically increased the amount of IgG1 in serum. In addition, ADC+ anti-PD-L1 dual treatment significantly increased the frequency of CD8+IFNγ+ cells in TILs. Both ADC alone (p=0.0004) and ADC+anti-PD-L1 dual treatment (p=0.01) significantly decreased CD4+FoxP3+ regulatory T cells. These results provide evidence that HER2-targeted ADC + anti-PD-L1 immunotherapy-induced B cell activation and differentiation along with the modulation of T cell subsets could confer host anti-HER2 immunity.
Citation Format: You Qin, Hannah E. Dobson, Frank I. Comer, Alfred E. Chang, Max S. Wicha, Qiao Li. Specific anti-HER2 host immunity conferred by HER2-targeted antibody drug conjugate therapy and checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 514.
Abstract 544: Urine as a non-invasive alternative to blood for germline and somatic mutation detection in hepatocellular carcinoma
Authors: Kim Amy , Lin Selena , Cui Yixiao , Gade Terence , Shieh Fwu-Shan , Chao Max , Shieh John , Jain Surbhi , Cheng Jonathan , Hamilton James , Hann Hie-Won L. , Goryunov Dmitry , Su Ying-Hsiu 
Published: July 2021

Abstract
BACKGROUND: Cell-free DNA (cfDNA) from blood has become a promising analyte for cancer diagnostics. However, because blood contains high concentrations of proteins and enzyme inhibitors, plasma cfDNA quality can be variable. Urinary cfDNA has been shown to contain mutations associated with non-genitourologic cancers including hepatocellular carcinoma (HCC). In this study, we evaluate urine as a noninvasive alternative to blood-based liquid biopsy for both germline and ctDNA genotyping in HCC.
METHOD: Using qPCR, whole-genome sequencing (WGS), and targeted NGS, DNA isolated from blood or urine of patients with HCC was evaluated and analyzed for overall genome coverage, HCC hotspot coverage, and germline or somatic mutation concordance. Targeted NGS of plasma and urine cfDNA was also performed for detection of somatic variants.
RESULTS: Similar to plasma cfDNA, urine cfDNA showed a major mononucleosomal species of 165-170 bp, with dinucleosomal species also discernable in most healthy individuals and patients with HCC. Overall genome coverage breadth was similar between urine and plasma cfDNA, with higher fraction of covered cancer-associated mutation hotspots in urine cfDNA. Quantitative PCR analyses of HCC-associated mutations (TP53, CTNNB1, and hTERT) in 102 patients with HCC, revealed 78% overall concordance between plasma and urine. Targeted NGS of HCC-associated gene regions in additional 15 patients showed an 97% overall position-level concordance between plasma and urine cfDNA. Furthermore, urine outperformed plasma in both the sensitivity and specificity of detection of CTNNB1 and hTERT mutations.
CONCLUSION urine DNA can potentially be used as a completely noninvasive diagnostic biomarker for HCC.
Citation Format: Amy Kim, Selena Lin, Yixiao Cui, Terence Gade, Fwu-Shan Shieh, Max Chao, John Shieh, Surbhi Jain, Jonathan Cheng, James Hamilton, Hie-Won L. Hann, Dmitry Goryunov, Ying-Hsiu Su. Urine as a non-invasive alternative to blood for germline and somatic mutation detection in hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 544.
Abstract 578: Comparative analysis of cell free DNA with whole-exome sequencing (cfWES) and application to personalized minimal residual disease (MRD) monitoring
Authors: Wang Amy Xiaohong , Zhao Zhixin , Dai Chao , Zhou Kemin , Jia Shidong , Du Pan , Luo Shujun 
Published: July 2021

Abstract
Liquid biopsy has become increasingly important in cancer diagnosis, personalized medicine, and disease progression monitoring. Conventional liquid biopsy relies on cancer gene panels which often contain fewer than 500 genes. Despite the revolutionary impact it has brought to the cancer research and cancer patient care, gene panels often miss many key mutations involved in cancer development and drug response. To fully capture the genetic variations embedded in cfDNA, we have developed Predicine-cfWES assay, which expands the features of our existing 152-gene PredicineCARE and 600-gene PredicineATLAS NGS panel with additional coverage of coding regions of the entire human genome. With 2500 x sequencing depth, Predicine-cfWES assay detects common cancer variants at sensitivity of 1% allele frequency and precisely measures copy number variations, such as loss of tumor suppressor genes (PTEN, BRCA2, p53) and gain of oncogenic driver genes (AR, Myc, ERBB2). Variants detected by Predicine-cfWES assay was confirmed by PredicineCARE panel based NGS assay and further used in tumor-agnostic personalized MRD assay. In conclusion, we have developed a comprehensive liquid biopsy solution to profile cfDNA with broad coverage of ~20,000 genes in the whole exome and higher sensitivity in a focused set of clinically actionable cancer variants for more personalized MRD monitoring in cancer patients.
Citation Format: Amy Xiaohong Wang, Zhixin Zhao, Chao Dai, Kemin Zhou, Shidong Jia, Pan Du, Shujun Luo. Comparative analysis of cell free DNA with whole-exome sequencing (cfWES) and application to personalized minimal residual disease (MRD) monitoring [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 578.
Abstract 581: Prognostic implication of circulating tumor-derived KRAS mutation in pancreatic ductal adenocarcinoma
Authors: Kim Min Kyeong , Lee Dong-Eun , Kim Yun Hee , Park Sang Jae , Woo Sang Myung , Kong Sun-Young 
Published: July 2021

Abstract
Circulating tumor DNA (ctDNA) has been evaluated as potential biomarkers for prognosis in pancreatic adenocarcinoma(PDAC) including our previous study, which proved KRAS mutation as a prognostic marker through the quantitative analysis. Then we investigated in a larger samples to validate the results of previous studies. Total of 213 PDAC patients has been enrolled in this study and the median age was 66 years old and 120 males (56.1%). Plasma was separated by established centrifugation method and ctDNA was extracted from 2.0 mL plasma using a QIAamp Circulating Nucleic Acid Kit (Qiagen Cat# 61504, Hilden, Germany) or a Chemagic cfDNA 2K kit (PerkinElmer, Waltham, Massachusetts, U.S.). Extracted ctDNA was quantified using the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific, USA). The detection of KRAS mutation was performed using QX200 Droplet Digital PCR System (Biorad, USA) by KRAS screening multiplex droplet digital PCR kit which covers seven common mutation sites (Biorad, USA) and compared with that in 93 matched formalin-fixed paraffin-embedded (FFPE) tissues. Mutant concentration and fractional abundance were analyzed by QuantaSoft software (Biorad, USA). The KRAS mutation rates in tissue and ctDNA were 98.9% and 82.8%, respectively, and the concordance rate between them was 78 of 93 samples (83.9%). Univariable analyses demonstrated that KRAS fraction (Hazard ratio (HR), 1.59; 95% CI, 1.02-2.49; P = 0.040) were significant factors for PFS, whereas KRAS mutation concentration (HR, 1.69; 95% CI, 1.03-2.77; P = 0.038) and KRAS fraction (HR, 1.88; 95% CI, 1.17-3.02; P = 0.010) for OS. This study proved the usefulness of the KRAS mutation of ctDNA as a prognostic marker in PDAC. (This study was supported by National cancer center, Korea, Grant no. 1910192)
Citation Format: Min Kyeong Kim, Dong-Eun Lee, Yun Hee Kim, Sang Jae Park, Sang Myung Woo, Sun-Young Kong. Prognostic implication of circulating tumor-derived KRAS mutation in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 581.
Abstract 584: Circulating tumor cells as prognostic biomarkers in glioblastoma
Authors: Bark Juliana Müller , Kulasinghe Arutha , Leo Paul , Hartel Gunter , Warkiani Majid E. , Jeffree Rosalind L. , Chua Benjamin , Day Bryan W. , Punyadeera Chamindie 
Published: July 2021

Abstract
Background: Glioblastoma (GBM) is the most common and aggressive type of tumor arising from the central nervous system. GBM remains an incurable disease despite current advancement in therapies, with survival rates of approximately 15 months. Recent literature has highlighted that GBM can release tumoral content which crosses the blood-brain barrier (BBB) and as a consequence can be detected in patients' blood, such as circulating tumor cells (CTCs). CTCs carry tumor information and have shown promise as prognostic and predictive biomarkers in other cancer types. Currently, the prognostic utility of CTCs in GBM is not well understood.
Methods: Blood samples from GBM patients (n=18) attending a tertiary referral hospital were collected before and after surgery to investigate the prognostic role of CTCs. CTCs were isolated using spiral microfluidic technology and characterized using immunofluorescence for GFAP, cell surface vimentin and CD45, in addition to fluorescence in situ hybridization (FISH) to detect EGFR amplification. CTC counts of patients with poor outcomes (recurrence or death) versus patients with good outcomes (stable disease and no recurrence) were compared using a negative binomial distribution.
Results: CTCs were found in 12 out of 18 patients (66.7%), 8/18 before surgery and 10/17 after surgery. CTC clusters were found in 2 patients. CTCs counts before surgery were significantly higher for patients with poor clinical outcome (p=0.0396).
Conclusion: Our preliminary data support the use of this spiral technology to isolate CTCs. CTCs and CTC clusters can be used as prognostic biomarkers for managing GBM patients.
Citation Format: Juliana Müller Bark, Arutha Kulasinghe, Paul Leo, Gunter Hartel, Majid E. Warkiani, Rosalind L. Jeffree, Benjamin Chua, Bryan W. Day, Chamindie Punyadeera. Circulating tumor cells as prognostic biomarkers in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 584.
Abstract 597: Comprehensive analysis of blood-based biomarkers to immunotherapy using circulating tumor cells, peripheral blood cells and circulating tumor DNA in advanced non-small cell lung cancer
Authors: Park Cheol-Kyu , Cho Hyun-Ju , Oh In-Jae , Kim Young-Chul 
Published: July 2021

Abstract
Background: This study aimed to investigate the feasibility of liquid biopsy using circulating tumor cells (CTCs), peripheral blood cells (PBCs) and circulating tumor DNA (ctDNA) as predictive blood-based biomarkers to immunotherapy in advanced non-small cell lung cancer (NSCLC).
Methods: This study included patients with advanced NSCLC receiving pembrolizumab or atezolizumab from July 2019 to June 2020. Blood was collected in K2-EDTA tube before each administration from cycle 1 to 4 (C1-4), and PBC counts (absolute neutrophil count[ANC], neutrophil-to-lymphocyte ratio[NLR], derived NLR[dNLR], platelet-to-lymphocyte ratio[PLR]) were calculated at each cycle. CTCs were enriched by using CD-PRIMETM system, the antibody-independent size-based isolation method, and identified by single positive cells (EpCAM/CK+CD45-) in BioViewCCBSTM system. Cell-free DNA was purified and extracted from plasma at baseline and C4 or end-of-treatment.
Results: Among 83 response-evaluable patients, objective response rate was 19% and durable clinical benefit (DCB) were 34%. Baseline (C1) CTC, PBC count and ctDNA amount did not show a significant difference according to best response and DCB. However, patients with lower NLR, dNLR, PLR and ctDNA level at C1 showed significant benefit in progression-free survival (PFS) and overall survival (OS) (p&lt;0.05 for all). Patients with decreased CTC at C2 compared to C1 showed benefit in median PFS (6.2 vs 2.3, p=0.078) and OS (not reached [NR] vs 6.8, p=0.021) than those with increased CTC count. Low dNLR (≤2.0) at C1 and decreased CTC at C2 compared to C1 were the independently significant factors for survival.
Conclusion: Comprehensive analysis of CTC, PBC count and ctDNA amount at baseline and their changes during treatment could be potential biomarkers to predict the survival benefit and may help risk-group stratification in patients with advanced NSCLC who received anti-PD-1/PD-L1 immunotherapy.
Citation Format: Cheol-Kyu Park, Hyun-Ju Cho, In-Jae Oh, Young-Chul Kim. Comprehensive analysis of blood-based biomarkers to immunotherapy using circulating tumor cells, peripheral blood cells and circulating tumor DNA in advanced non-small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 597.
Abstract 647: CXCL17 as a prognostic biomarker for aggressive cutaneous squamous cell carcinoma
Authors: Fermin Janmaris Marin , Alam Maksudul MD , Gu Xin , Asarkar Ameya , Nathan Cherie-Ann , Khandelwal Alok R. 
Published: July 2021

Abstract
Cutaneous squamous cell cancer (cSCC) is one of the most rapidly increasing cancers in the USA, striking 200,000 Americans annually. cSCC is most often observed in the sun-exposed areas such as the head and neck region. Although most patients have an improved prognosis after surgical treatment, a subset carries an increased risk of local recurrence, nodal metastasis, and disease-specific death. CXCL17 (C-X-C Motif Chemokine Ligand 17) is the latest chemokine family member, and our preliminary studies identified a causative role of CXCL17 in skin tumorigenesis. Accordingly, we aimed to investigate the correlation between CXCL17 and clinicopathological factors associated with recurrence, metastasis, and disease-specific death in cSCC. A retrospective chart review was conducted to identify patients with cSCC at Louisiana State University Health Sciences Center Shreveport (LSUHSC-S) and Overton Brooks Veterans Affairs Medical Center. Tissue samples were immunostained for human CXCL17/VCC-1. Risk factors such as the depth of invasion, perineural invasion, tumor diameter, location, and differentiation were obtained from chart review/clinical databases and correlated with the expression of CXCL17. Among 42 subjects included in the analysis, the Histo-score of CXCL17 expression in cytoplasm and nucleus was higher in the malignant group compared to the normal skin group (p=0.01 and p=0.03, respectively). Interestingly, the Histo-score of CXCL17 expression was associated with perineural invasion (p=0.01) suggesting a role for CXCL17 in disease aggressiveness. Our results indicate a positive correlation between CXCL17 and cSCC aggressiveness. Increased expression of CXCL17 was associated with perineural invasion, a principal risk factor for recurrence, metastasis, and disease-specific death in cSCC patients. These results suggest that CXCL17 plays a role as a prognostic marker and warrants further exploration as a potential target for treatment in aggressive cSCC.
Citation Format: Janmaris Marin Fermin, Maksudul MD Alam, Xin Gu, Ameya Asarkar, Cherie-Ann Nathan, Alok R. Khandelwal. CXCL17 as a prognostic biomarker for aggressive cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 647.
Abstract 664: Development and validation of a glycolysis-related gene signature to predict overall survival in lung adenocarcinoma patients
Authors: Wang Shengguang , Bei Zhang 
Published: July 2021

Abstract
Background: Genomic expression profiles have enabled the classification of lung adenocarcinoma (LUAD) into molecular sub-types and provide prognostic information, which have implications for the personalized treatment of LUAD beyond clinical and pathological features.
Methods: Gene-expression profiling was performed on 459 patients in TCGA-LUAD(I-IIIa) for which RNA sequencing data and clinical covariates were available. A single-sample gene set enrichment analysis (ssGSEA) algorithm were used to quantified the levels of various hallmarks of cancer. And LASSO Cox regression model was used to screen robust prognostic biomarkers to identify the best set of survival-associated gene signatures in LUAD. Statistical analyses were performed using R version 3.4.4.
Results: We identified glycolysis as the primary risk factor for survival(HR=0.55 [0.38-0.8], P&lt;0.001)among various hallmarks of cancer in TCGA-LUAD. And glycolysis ssGESA scores were significantly elevated in patients who died during follow up (P&lt;0.001). Kaplan-Meier analysis showed that patients with high ssGSEA scores of glycolysis exhibited worse OS ( HR=1.9,P= 0.001).Adjusted for stage,age,gender, our signature was an independent risk factor for overall survival in TCGA cohorts (HR=1.67[1.19-2.30],P= 0.003). We then apply the glycolysis -related gene signature to classify patients into the high risk group and the low risk group with the cutoff of median. In external independent cohorts, similar results were observed. In the validation cohort GEO31210, the multivariate Cox regression analysis showed that glycolysis -related gene signature exhibited an independent risk prediction for overall survival in 226 patients with stage I-II LUAD (HR=2.5 [1.11-5.5], P =0.025).
Conclusions: By analyzing the gene-expression data with bioinformation approach, we developed and validated a risk prediction model with glycolysis -related expression scores in early stage LUAD, which have the potential to identify patients who could have better overall survival. Furthmore, our study confirmed that tumor glycolysis has wide-ranging effects, would become an attractive therapeutic target.
Citation Format: Shengguang Wang, Zhang Bei. Development and validation of a glycolysis-related gene signature to predict overall survival in lung adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 664.
Abstract 684: Effects of preventive interventions on radiotherapy-induced skin toxicity in women with breast cancer: A systematic review and meta-analysis of randomized controlled trials
Authors: Figueroa Claudia R. , Gelin Rose N. , Khourshid Sereen J. , Lee Eunkyung 
Published: July 2021

Abstract
Radiation therapy (RT)-induced skin toxicity occurs in 95% of patients undergoing RT for breast cancer. Severe cases can interrupt the original treatment regimen and affect many individuals' overall treatment efficacy and quality of life. Many interventions have been tested for the prevention of RT-induced skin toxicity; however, there are no standard recommendations yet determined. This meta-analysis aimed to evaluate the effect of different preventive interventions for RT-induced skin toxicity among breast cancer patients. We searched PubMed, Web of Science, CINAHL, and PsycINFO databases for randomized controlled trials (RCTs) meeting the inclusion criteria and published until December 2019 following the PRISMA reporting guidelines and the PICO statements. The intervention's effect on the incidence of grade ≥2 acute skin toxicity, moist desquamation, and severity score was estimated using the random-effects meta-analyses. Among 6885 publications identified, 38 studies were included in analyses. A total of 3,380 women age 42-88 years diagnosed with stage 0-III who were undergoing RT for breast cancer from all over the world were included. Identified preventive interventions included non-steroid topical agents, topical steroid agents, oral supplements, laser therapy, and films. The meta-analyses showed that interventions significantly reduced the mean severity score by 0.64 (standardized mean difference=-0.64, 95% CI=-0.85, -0.43; I2=57.6%), the incidence of grade ≥2 skin toxicity by 18% (Risk ratio [RR]=0.82, 95% CI=0.74, 0.90; I2=68.4%), and moist desquamation by 55% (RR=0.45, 95% CI=0.27-0.77, I2=48.2%). Subgroup analyses showed that oral supplements were most promising in preventing grade ≥2 skin toxicity (RR=0.32, 95% CI=0.07-1.34, I2=83.1%), suggesting further replications are needed before definitive conclusions are made. This analysis provided evidence of the effectiveness of interventions on the prevention of RT-induced skin toxicity. The effect was greater in reducing the incidence of more severe cases of moist desquamation. More replicative studies are needed to establish the standard preventive care of RT-induced skin toxicity for women with breast cancer, which can help patients comply with RT regimens and improve patients' quality of life.
Citation Format: Claudia R. Figueroa, Rose N. Gelin, Sereen J. Khourshid, Eunkyung Lee. Effects of preventive interventions on radiotherapy-induced skin toxicity in women with breast cancer: A systematic review and meta-analysis of randomized controlled trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 684.