bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3303: Development and initial validation of a prognostic score based on structured data from EHRs
Authors: Backenroth Daniel , Haimson Josh D. , Meropol Neal J. , Baxi Shrujal S. 
Published: August 2019

Abstract
Introduction
Real world data (RWD) is increasingly used to supplement clinical trial data. Prognostic scores (PS) such as ECOG performance status (ECOG) are important for matching patient populations and assessing treatment impact, yet such PS are often missing from patient records or are embedded in physician narratives. An accurate PS that does not rely on physician assessment or data entry would have broad utility. We therefore undertook development of a PS based solely on structured data from RWD across numerous cancer diagnoses (the structured PS). We then sought initial validation of the structured PS in patients treated with checkpoint inhibitors (CIT).
Methods
Using the Flatiron Health electronic health record-derived database, we applied LASSO regression to develop the structured PS to predict for overall survival (OS) after starting any first-line (1L) cancer therapy. Data included laboratory values and vital signs from between 30 days before and 15 days after start of treatment as well as age. The structured PS was developed from ~39K patients with multiple myeloma, chronic lymphocytic leukemia or one of 8 solid tumor malignancies. We evaluated the structured PS using concordance, i.e., how often the score correctly predicts the relative OS of two randomly selected patients, on ~24K patients, comparing to a baseline based on age and ECOG, when available. We then measured the association of OS with the structured PS at start of 1L CIT in patients with five tumor types where 1L CIT is common.
Results
The concordance of the structured PS was 66%-73%, on average 6% higher than that of age and ECOG.
Table 1 shows by cancer type # of patients and median OS from 1L CIT for quartiles of the structured PS (NR=not reached).
Conclusion
A structured PS can be an important pan-tumor variable in investigations of OS using RWD, including for patients treated with first-line CIT.
OS from 1L CIT by quartiles of structured PSDiseasenQ1 median (95% CI) in monthsQ2 median (95% CI) in monthsQ3 median (95% CI) in monthsQ4 median (95% CI in months)Head and neck3704 (3-5)9 (7-12)14 (12-Inf)NR (NR-Inf)Melanoma16355 (4-6)20 (15-26)33 (22-Inf)NR (NR-Inf)Non-small cell lung cancer41714 (3-4)9 (8-10)14 (13-16)24 (21-29)Renal cell carcinoma2775 (3-7)23 (12-Inf)20 (13-Inf)NR (28-Inf)Urothelial cancer6122 (2-3)6 (4-7)9 (7-13)NR (15-Inf)
Note: This abstract was not presented at the meeting.
Citation Format: Daniel Backenroth, Josh D. Haimson, Neal J. Meropol, Shrujal S. Baxi. Development and initial validation of a prognostic score based on structured data from EHRs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3303.
Abstract 3324: Non-invasive detection of aberrant DNA methylation in colorectal cancer by multiplex methylation specific PCR
Authors: Ye Lili , Zheng Chunting , Jie Yuan , Li Bin , Li Yuan , Hu Kunling , Zeng Liuhong , Wang Yuying , Mao Mao , Ding Peirong , Shi Taiping , Ye Mingzhi 
Published: August 2019

Abstract
Colorectal cancer (CRC) is a leading cause of morbidity and mortality worldwide, with an increasing prevalence. The 5-year relative survival rate for advanced stages is very low, with only 14% for stage IV. However, that of the early stage of CRC is about 90%. Therefore, it is important to screen CRC in the early stage. Epigenetic alterations linked to the carcinogenesis of CRC have been shown to occur earlier and more frequently than genetic alterations in CRC. Here, our study aims to develop a CRC screening methodology by applying the multiplex methylation specific PCR (MMSP) assay to detect CRC-specific methylation biomarkers, which has been pre-selected from public databases and subsequently validated in CRC samples of the Chinese population. Experimentally, cell free DNA (cfDNA) is extracted from ~4ml peripheral blood plasma. Following bisulfite conversion of the cfDNA, MMSP were applied to amplify and detect CRC-specific methylated CpG sites within the cfDNA. From the results of 28 CRCs and 52 control specimens, a sensitivity of 85.7% and the a specificity of 92.3% was achieved. Current standard and most widely used method of detecting CRC is colonoscopy screening. However, colonoscopy requires bowel preparation, and the sedation for patients is a complex and time-consuming procedure with high cost. Additionally, this invasive method also increases the possibility of infection and complications and patient compliance still largely remains a problem. Our non-invasive MMSP assay therefore provides an alternative non-invasive screening option that is cost-effective, meeting the urgent demand of early CRC detection. In addition, because colonoscopy screening currently has low adherence in Chinese population, our method holds great potential for increasing CRC screening rate in China.
Citation Format: Lili Ye, Chunting Zheng, Yuan Jie, Bin Li, Yuan Li, Kunling Hu, Liuhong Zeng, Yuying Wang, Mao Mao, Peirong Ding, Taiping Shi, Mingzhi Ye. Non-invasive detection of aberrant DNA methylation in colorectal cancer by multiplex methylation specific PCR [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3324.
Abstract 3339: Ethnic disparity in ovarian malignancy tumor markers: MIA and ROMA
Authors: Dunton Charles , Fritsche Herbert , Bullock Rowan 
Published: August 2019

Abstract
Objective: Review and analyze serum values of Risk of Ovarian Malignancy Algorithm (ROMA) and Multivariate Index Assay (MIA) in subgroups of women who underwent surgery for adnexal masses to determine sensitivity in different ethnic populations.
Methods: Serum samples from 179 women diagnosed with ovarian malignancy were analyzed for ROMA and MIA results. Biomarker data was obtained from previous prospective studies that validated the MIA test. Of these, 167 women were Caucasian (C) and 12 African-American (AA) in the MIA testing. Sample for ROMA included 161 C and 11 AA. Sensitivity (true positive rate) for preoperative test results were calculated using DTCompair package of the R programming language. In premenopausal women, a risk of ovarian malignancy algorithm (ROMA) value equal to or greater than 1.14 indicates a high risk of finding epithelial ovarian cancer. In premenopausal women, MIA values of greater than 5.0 are associated with greater risk of malignancy.
In postmenopausal women, a ROMA value equal to or greater than 2.99 indicates a high risk of finding epithelial ovarian cancer.
In postmenopausal women, MIA values of greater than 4.4 are associated with greater risk of malignancy.
Results: Primary ovarian malignancy was diagnosed in 179 cases (167 C/12 AA).
Sensitivity testing results are seen for each subgroup and for MIA levels and CA125 results:
Primary Ovarian Malignancy: Caucasian MIA 97.0%, ROMA 89.4%, AA MIA 75.0% ROMA 45.5%.
Sensitivity of ROMA in AA premenopausal women was 50% and in postmenopausal women 33.3 %.
Conclusion: Our results demonstrate that ROMA in both C andAA women with adnexal masses have lower sensitivity for detection of malignancy than does MIA. It is more pronounced in AA women. Implementation of MIA in evaluation of adnexal masses will increase sensitivity of detection of malignancy compared to CA125 testing, with most marked results in AA women.
Key Words: Ethnicity, CA125, and Multivariate Index Assay
Sensitivity of MIA vs. ROMA Ovarian MalignancyRaceTestStatusMenopauseNumberSensitivityCaucasianMIAAll16797.0CaucasianMIAPre4395.3CaucasianMIAPost12497.6CaucasianROMAAll16189.4CaucasianROMAPre4092.5CaucasianROMAPost12188.4African AmericaMIAAll1275African AmericaMIAPre977.8African AmericaMIAPost366.7African AmericaROMAAll1145.5African AmericaROMAPre850.0African AmericaROMAPost333.3
Citation Format: Charles Dunton, Herbert Fritsche, Rowan Bullock. Ethnic disparity in ovarian malignancy tumor markers: MIA and ROMA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3339.
Abstract 3345: Making the link between breastfeeding and breast cancer risk reduction among Hispanic women of childbearing age
Authors: Sondgeroth Karoline , Ruiz-Holguin Rosalba , Padilla Joe , Ramos Rebeca , Palacios Rebecca 
Published: August 2019

Abstract
Background/Purpose. Breast Cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer related deaths for women in Texas (TX). In the border county of El Paso, TX, the breast cancer incidence and mortality rates are higher for Hispanic women relative to all races combined. Evidence indicates that breastfeeding can be protective against BC by (1) limiting breast cells’ ability to act abnormally, (2) lowering estrogen levels, and (3) promoting healthier lifestyle choices. Research also indicates that the longer a woman breastfeeds, the lower her risk of developing BC. Unfortunately, among all infants born in TX in 2015, only 48% were exclusively breastfed for up to 3 months and only 24.1% were exclusively breastfed for up to 6 months. The goal of the Breastfeeding Breast Cancer Connection Program (BFBCCP) is to increase intent to breastfeed among Hispanic women of childbearing age (18-44 years) by providing a brief education intervention focused on the importance of breastfeeding and BC prevention.
Methods. Study participants included 50 Hispanic women of childbearing age living at the El Paso Housing Authority in El Paso, TX. The study consisted of an intervention group (n=25) and a control group (n=25). The control group received only educational brochures about breastfeeding, whereas, the intervention group received an educational presentation about the importance of breastfeeding and BC prevention. Measures assessed in this study included: 1) knowledge of breastfeeding and BC 2) attitudes towards breastfeeding in the workplace, and 3) behavioral intentions to breastfeed. All measures were assessed via a pre and post self-report survey in the participants preferred language.
Results/Findings. Overall, Hispanic women participating in the BFBCCP learned more about the importance of breastfeeding, particularly as it relates to BC prevention, reported greater levels of intent to breastfeed, and reported more positive attitudes towards breastfeeding in the workplace compared to the control group. Given their high BC incidence and mortality rates, Hispanic women in the TX border region would benefit from interventions like BFCCP that promote exclusive breastfeeding for a duration of six mos. to one year as a means of reducing their BC risk. The next step is to assess the efficacy of the BFCCP in increasing breastfeeding completion and duration among pregnant Hispanic women.
Citation Format: Karoline Sondgeroth, Rosalba Ruiz-Holguin, Joe Padilla, Rebeca Ramos, Rebecca Palacios. Making the link between breastfeeding and breast cancer risk reduction among Hispanic women of childbearing age [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3345.
Abstract 3361: A prescription for new trial designs for drug development focused on the neoadjuvant setting: Save lives, resources, and time
Authors: Karlsson Andreas , Shieh Yiwey , Dempsey Andre , Yau Christina , Dmichele Angela , Yes Doug , Veer Laura van't , Hylton Nola , Eklund Martin , Esserman Laura 
Published: August 2019

Abstract
Background: Traditionally, new drug combinations are first tested for safety and efficacy in the stage 4 setting. The I-SPY 2 TRIAL has focused on bringing promising new combinations into the phase 2/3 high-risk setting once safety is established. I-SPY 2 is an adaptive neoadjuvant platform trial for women with stage 2/3 breast cancer at high risk for early recurrence. In this setting, complete pathologic response (pCR) is the primary endpoint. We and others have demonstrated that pCR is highly predictive of distant recurrence free survival at 3 years. In I-SPY 2 the hazard rate is 0.2 (Confidence Interval 0.11-0.37), regardless of subtypes or agent. Agents that extend progression free survival in the metastatic setting, can be lifesaving when given at an earlier stage setting.
Methods: The health economic benefits of achieving pCR were investigated using a Markov model describing the risk of recurrence, progression and death. The risk of recurrence was informed by I-SPY 2 and the risk of cancer progression and the associated treatment costs were based on literature values. We assumed constant recurrence rate without accounting for subtype specific rates in this first version of the model.
Results: For each additional patient with pathologic complete response a net monetary benefit of $170,000 (Credible Interval 95% 100,000—250,000) and a gain of 4 life-years (CrI 95% 2—6) was predicted. The ICER for pCR is -$45,000. This represents the aggregate benefit across all I-SPY cancers. Modeling accounting for cancer subtype is in process and will be presented also.
Conclusion: A short term endpoint, response to chemotherapy in the neoadjuvant setting, which is highly correlated with long term outcome, provides the opportunity to focus drug development on improving that endpoint. Enabling more patients to achieve a pCR would provide enormous benefit in terms of lives and resources saved. The economic modeling, along with the findings from I-SPY 2 suggests that we should shift drug development to the high risk early setting and evolve drug designs to improve every patient’s outcome. In I-SPY 2, we are shifting our platform trial design to increase every patient’s chance to achieve pCR. Platform adaptive trials in the early stage neoadjuvant setting are ideal for advancing the field and maximizing benefit for patients.
Citation Format: Andreas Karlsson, Yiwey Shieh, Andre Dempsey, Christina Yau, Angela Dmichele, Doug Yes, Laura van't Veer, Nola Hylton, Martin Eklund, Laura Esserman. A prescription for new trial designs for drug development focused on the neoadjuvant setting: Save lives, resources, and time [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3361.
Abstract 337: Degradation of AXL overcome acquired cross-resistance to gefitinib and osimertinib in non-small cell lung cancer cells
Authors: Kim Donghwa , Bach Duc-Hiep , Fan Yan-hua , Luu Thi-Thu-Trang , Hong Ji-Young , Park Hyen-Joo , Lee Sang Kook 
Published: August 2019

Abstract
Epidermal growth factor receptor (EGFR) mutation is one of the major driver oncogenes in non-small cell lung cancer (NSCLC) and most frequently found in Asian patients. Although the first generation of EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have led to improved prognoses for NSCLC patients, acquired resistance has been a major obstacle in the treatment of non-small cell lung cancer (NSCLC) patients. Recently, AXL has been reported to play a role in drug resistance mechanisms for many anti-cancer drugs, including erlotinib and cetuximab, as well as in ionizing radiation therapy for multiple cancers. In the present study, we demonstrate the involvement of AXL in the acquired resistance to gefitinib and osimertinib of EGFR-mutant NSCLC cells, then show the combination effect of an AXL degrader and EGFR-TKIs to overcome EGFR-TKIs-driven resistance in EGFR-mutant NSCLC cells. We found that AXL was overexpressed and its degradation was delayed in EGFR-TKI-resistant NSCLC cells. Yuanhuadine (YD), a natural antitumor agent, effectively suppressed the expression of AXL by accelerating protein degradation. YD combined with gefitinib or osimertinib synergistically inhibited the growth of resistant cells in vitro and suppressed tumor growth in a nude mouse xenograft model. Moreover, administration of YD with gefitinib effectively delayed gefitinib-driven acquired resistance in a long-term xenograft model. Our results suggest that the combination of YD with either gefitinib or osimertinib is a potentially effective treatment strategy for overcoming and delaying acquired resistance in NSCLC by targeting AXL degradation.
Citation Format: Donghwa Kim, Duc-Hiep Bach, Yan-hua Fan, Thi-Thu-Trang Luu, Ji-Young Hong, Hyen-Joo Park, Sang Kook Lee. Degradation of AXL overcome acquired cross-resistance to gefitinib and osimertinib in non-small cell lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 337.
Abstract 3370: Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers
Authors: Osmanbeyoglu Hatice Ulku , Shimizu Fumiko , Rynne-Vidal Angela , Yeung Tsz-Lun , Jelinic Petar , Mok Samuel C. , Chiosis Gabriela , Levine Douglas A. , Leslie Christina 
Published: August 2019

Abstract
Epigenomic data on transcription factor occupancy and chromatin accessibility can elucidate the developmental origin of cancer cells and reveal the enhancer landscape of key oncogenic transcriptional regulators. We develop a computational strategy called PSIONIC (patient-specific inference of networks informed by chromatin) to combine cell line chromatin accessibility data with large tumor expression data sets and model the effect of enhancers on transcriptional programs in multiple cancers. We generated a new ATAC-seq data set profiling chromatin accessibility in gynecologic and basal breast cancer cell lines and applied PSIONIC to 723 patient and 96 cell line RNA-seq profiles from ovarian, uterine, and basal breast cancers. Our computational framework enables us to share information across tumors to learn patient-specific TF activities, revealing regulatory differences between and within tumor types. Many of theidentified TFs were significantly associated with survival outcome in basal breast, uterine serous and endometrioid carcinomas. To validate one PSIONIC-derived prognostic TF, we performed immunohistochemical analyses in 31 uterine serous tumors for ETV6 and confirmed that the corresponding protein expression pattern was also significantly associated with prognosis. Moreover, PSIONIC-predicted activity for MTF1 in cell line models correlated with sensitivity to MTF1 inhibition, showing the potential of our approach for personalized therapy.
Citation Format: Hatice Ulku Osmanbeyoglu, Fumiko Shimizu, Angela Rynne-Vidal, Tsz-Lun Yeung, Petar Jelinic, Samuel C. Mok, Gabriela Chiosis, Douglas A. Levine, Christina Leslie. Chromatin-informed inference of transcriptional programs in gynecologic and basal breast cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3370.
Abstract 3379: Assessment of tumor mutation burden using a novel panel design strategy utilizing highly mutated genomic regions
Authors: Pati Amrita , Klass Daniel , Huang Zhongyun , Loyzer Melissa , Lovejoy Alex 
Published: August 2019

Abstract
Background
Tumor Mutation Burden (TMB) has grown in importance as a predictive biomarker for predicting response to check-point immunotherapy in several cancer disease areas such as non-small cell lung cancer (NSCLC) and melanoma. Although TMB derived from analysis of WES data is the current gold standard measure of the number of neoantigens in the system, WES is often cost-prohibitive as a routine practice for clinical interpretation. Targeted panels offer a more flexible and cost-effective option, but TMB estimates based on these subsets of the exome can be more variable and often disagree with each other. Current best practices for TMB panels advocate for panels with sizes of 1 Mb with high correlation between panel-derived TMB and WES TMB demonstrating effectiveness of a panel at assessing TMB accurately.
Methods
We present a systematic approach to designing panels for detecting TMB effectively while minimizing cost of sequencing, based on our Surveillance panel design algorithm. Our approach relies on the prioritization of highly recurrent non-driver mutations present in large cohorts (such as TCGA) for disease areas of interest. Such an approach greatly boosts the number of observations of short variants using a targeted panel while still meeting expectations outlined within current best practices such as a high correlation with WES-derived TMB, and high PPA and NPA with WES-derived TMB. Our NGS based workflow combines whole genome library preparation, hybrid capture target enrichment, high-throughput sequencing and a proprietary analysis algorithm that utilizes short exonic variants that are likely to be somatic.
Results
Using a combination of in silico data and clinical cohorts, we demonstrate the effectiveness of the above approach in designing panels for the assessment of TMB. Results show high correlations between panel-derived TMB and WES-derived TMB at panel sizes as low as 450Kb while highlighting the steady decrease in variability of the TMB score as panel size increases. We apply this panel and WES analysis to clinical NSCLC and CRC samples to demonstrate that recommendations from current best practices are met in terms of PPA and NPA with WES-derived TMB and high correlation with WES-derived TMB.
Citation Format: Amrita Pati, Daniel Klass, Zhongyun Huang, Melissa Loyzer, Alex Lovejoy. Assessment of tumor mutation burden using a novel panel design strategy utilizing highly mutated genomic regions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3379.
Abstract 3380: Methylome analysis of non-alcoholic fatty liver disease-associated hepatocellular carcinoma reveals etiology-specic pathway perturbations
Authors: Wu Qiong 
Published: August 2019

Abstract
Chronic hepatitis B infection (HBV) and non-alcoholic fatty liver disease (NAFLD) have been shown to induce aberrant DNA methylation that may contribute to the development of hepatocellular carcinoma (HCC), which is one of the most common liver cancers. Most previous studies on DNA methylation in HCC have focused on altered methylation at gene promoters and CpG islands/shores. However, it has been increasingly recognized that DNA methylation in other genomic regions, including distal enhancers and gene bodies, could also play important roles in gene regulation in cancers. In our whole-genome bisulfite sequencing (WGBS) analysis of 10 human HBV-associated tumors and 10 human NAFLD-associated tumors, methylation states at all CpG sites in the genome of HCC tumors are comprehensively studied. To see how the methylomes of these two groups of HCC samples are related to other liver-related normal and pathogenic samples, we collected published WGBS data for HCC tumor, tumor adjacent and normal liver samples. Global hypermethylation of NAFLD-HCC has been identified compared with HBV-HCC and differentially methylated regions in enhancer and gene body regions also have been detected. Different methylation patterns for HCC pathogenesis with different etiologies have been detected and may offer potentially more specific therapeutic targets. This project is supported by Collaborative Research Fund C4017-14G and the Focused Innovations Scheme 1907309.
Citation Format: Qiong Wu. Methylome analysis of non-alcoholic fatty liver disease-associated hepatocellular carcinoma reveals etiology-specic pathway perturbations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3380.