bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world evidence evaluating the use of single versus combination chemotherapy in salvage therapy for metastatic breast cancer.
Authors: Feinberg Bruce A. , Lord Kevin , Kish Jonathan , Laney Jalyna R. , Chopra Dhruv , Liassou Djibril 
Published: May 2019

e12600 Background: Metastatic breast cancer (mBC) patients often receive multiple lines of systemic chemotherapy (Chemo) to extend life, manage disease symptoms and improve quality of life. Combination chemotherapy (cChemo) provides no survival advantage over single agent sequential chemotherapy (sasChemo) in mBC, but it may increase the risk of toxicity and adverse events while decreasing quality of life. The National Comprehensive Cancer Network guideline states that sasChemo is preferred for recurrent or stage IV mBC. This study aimed to explore adherence to this recommendation by evaluating contemporary real-world treatment patterns in mBC. Methods: Patients were identified from a third-party, administrative claims database. Using medical and pharmacy claims, any female with mBC (both BC and metastatic ICD9/10 codes) diagnosed between 01-Jan-2013 and 31-Dec-2017, followed for at least 6 months, and who had initiated systemic therapy was selected. Patients who received any HER2 targeted therapy, any oral or infused hormonal therapy, and/or had other malignant diagnoses were excluded. The proportion of patients receiving each line of chemotherapy was calculated in addition to the proportion of sasChemo and cChemo. Results: 10,342 patients met the selection criteria. Mean age at initiation of treatment was 61.7 years (SD = 12.12), 35.7% of patients had Medicare/Medicare advantage insurance coverage. All patients received first line (1L) systemic chemotherapy, 59% received 2L, 39% 3L, 25% 4L, 16% 5L, and 12% 6L respectively. 4 patients received ≥ 7L. The distribution between sasChemo vs cChemo was 50%/50% in 1L, 42%/58% 2L, 43%/57% in 3L, 44%/56% in 4L, 45%/55% in 5L and 46%/57% in 6L. Conclusions: Despite medical evidence which resulted in clinical guideline preference for sasChemo, cChemo use continues to have significant use in the salvage treatment of mBC. Research is warranted to understand and lessen this low value practice.
Predictive molecular tumor response through circulating DNA (cDNA) measurements and correlation with established prognostic markers in a series of solid tumors treated with multitargeted epigenetic therapy (MTET).
Authors: Nezami Mohammad A. , Klowsowski Christian , Hager Steven Jeffrey 
Published: May 2019

e13015 Background: Epigenetic dysregulation of certain genes contribute to the progression of cancers. Plasma ctDNA concentrations can reflect these altered genes and have been shown to correlate well with tumor burden. Methods: We planned to assess the correlation value of c DNA on known factors for prediction of overall survival (OS), recognized as surrogates for survival. Ten( 10) genes of interest, namely NOTCH1, FGF2, MYC, RB1, ATM, MET, BRCA1, BRCA2, ATM and, VHL, were selected as being highly influenced by epigenetic control. We included 54 patients with reported cDNA on the genes of interest for this study evaluating the predictive impact of early changes in cDNA in response to multitargeted epigenetic treatment and the patient survival. There were 12 cases with NOTCH1 mutations, 20 cases with MYC mutations, 5 cases with RB1, 15 cases with BRCA1 or BRCA2 mutations, 26 cases with FGF2 mutations, 18 cases with MET mutations, 2 with VHL mutations and 2 cases with ATM mutations, for a total of 100 data points. Tests for statistical significance were completed using the Fisher Exact probability test calculator found at vassarstats.net/tab2x2.html. Significance level was set at α = .05. Results: There was statistically significant (p-value: .046) correlation on the response of the allele frequency of the observed NOTCH1 alteration with similar response in the angiogenesis biomarkers (Plasma VEGF) and presence of circulating tumor cells. There was a significant correlation (p-value: .014) between a decrease in AF of the observed MYC alteration and biomarker/imaging response on follow-up. In the group of 26 identified with FGF2 mutations, 22 saw cDNA alteration fraction(AF) reduction post therapy. 16/26 of them had either c Myc or NOTCH1 alterations. Also 8 /18 cases with c Met alterations shared NOTCH1 or Myc alteration. This represents a statistically significant (p-value: .0001) correlation on the response of the allele frequency of the observed FGFR2 alteration with the response of other biomarkers. Conclusions: There were a number of significant correlations observed between early changes in cDNA allele fractions of specific genes and the later observations of established prognostic markers. We conclude that changes in cDNA mutated allele fractions observed in liquid biopsy may provide an early useful independent prognostic marker for tumors carrying epigenetically influenced targets and their alterations.
Mutational analysis of key genes in patients from the Kazakh population with early onset of breast cancer.
Authors: Kaidarova Dilyara , Omarbayeva Nazgul , Zhunussova Gulnur , Abdrakhmanova Aliya , Abdikerim Saltanat , Djansugurova Leila 
Published: May 2019

e13038 Background: Breast cancer (BC) represents the most common malignancy and has the highest mortality among women, both in the world and in Kazakhstan. Approximately 20-30% of cases of hereditary BC are caused by presence of BRCA1/2 genes defects. Also, there are additional genes which can increase the risk of BC and they are still under study.The aim of this study was to identify new, detectable and objective markers of key cancer genes by next-generation sequencing (NGS) of young BC patients. Methods: Blood was collected from 129 BC patients (average age 34.87±5.587). DNAs were extracted using GeneJET Genomic DNA Purification Kit. NGS was done on the MiSeq platform using TruSightCancer Kit. NGS data were analyzed by the MiSeq Reporter v. 2.4 software. Variant annotation and interpretation was done by Variant Studio 3.0 software. Results: We perform the NGS and did the detailed bioinformatics analysis of sequences of 16 key genes of BC (BRCA1/BRCA2, BRIP1, ATM, CDH1, CHEK2, NBN, NF1, PALB2, STK11, TP53, RAD51C, RAD51D, BARD1, MUTYH and FANCC). At all 3016 variants were detected, 1080 (35.8%) out of which were missense; 1494 (49.5%) synonymous; 17 (0.6%) frameshifts; 2 (0.06%) inframe deletions, 8 (0.3%) stop gained; 4 (0.1%) splice variant, 411 (13.6%) intron or non-coding variants. We identified 24 pathogenic and likely pathogenic mutations in 31 patients (24% of all patient cohort), 3 mutations are novel. All mutations were in heterozygous state and were rare or had frequency data not available (NA) in 1000G, ESP6500and ExAC databases. Analysis of mutation type revealed 17 frameshift mutations, 2 missense mutations, 8 stop gained mutations, 4 mutations involving uncorrected splicing. Out of the 31 pathogenic and likely pathogenic variants, were detected 14 in BRCA1, 9 in BRCA2, 4 in TP53 genes, 3 in PALB2 and 1 in NBN. (BRCA2: c.6468_6469delTC, c.7567_7568delCT, c.9976A > T, c.8174G > A, c.2442delC, c.2808_2811delACAA, c.9253delA, c.9409dupA and c.6058G > T; BRCA1: c.2498delT, c.5224C > T, c.3020C > G, c.3352C > T, c.5530+1G > A, c.5341-2delA and BRCA1-c.5329dupC in 6 cases; NBN: c.657_661delACAAA; PALB2: c.172_175delTTGT, c.1034T > G and c.18_22delGAAGC; TP53- c.156dupA, c.1024C > T, c.844C > T and c.584T > C). The most frequent genes were BRCA1 (45%) and BRCA2 (29%). Conclusions: The study focused on identifying mutation profile of early onset BC using NGS. Clinically significant variants was detected which are promising biomarkers for the successful diagnosis and therapy of BC at women in reproductive age.
Germline DNA damage repair gene alterations in Chinese prostate patients: More than HRR and MMR.
Authors: Wu Junlong , Wei Yu , Zhu Changbin , Dai Bo , Qin Xiaojian , Gao Fangzhu , Ye Dingwei , Zhu Yao 
Published: May 2019

e13041 Background: Prostate cancer is a worldwide most occurred malignancy in male population. Genetic aberrations of homologous recombination repair (HRR) pathway were proved to be associated with aggressive disease and poorer outcome but may also lead cancer cells more vulnerable to PARP inhibitors. Other than HRR, germline variants in mismatch repair (MMR), nucleotide excision repair (NER) were also identified. Thus, it is important to clarify the distribution of germline alterations of DDR pathways in Chinese prostate cancer patients. Methods: Sixty-five prostate cancer patients unselected for family history, stage of disease, or age at diagnosis were collected. DNA from peripheral blood was extracted. Whole-exon was captured and sequenced subsequently using MGI-SEQ 2000 platform. A total of 229 DDR genes were selected for further analysis. Germline variants were determined to be deleterious according to the ACMG 2015 guidelines. Results: Ten of 65 patients (15.38%) had 7 pathogenic/likely pathogenic germline variants involving 5 different genes: FANCD2 (n = 5), BRCA2 (n = 3), CHEK2 (n = 1), ATM (n = 1) and RECQL (n = 1). Nine patients (13.84%) carried variants predicated to be deleterious via in silico predicators. Taken together, deleterious/potential deleterious germline variants were categorized into 5 DDR pathways which were Fanconi Anemia (9.2%), HRR (9.2%), MMR (4.6%), BER (4.6%) and NER (1.5%). Patients with pathogenic/likely pathogenic germline variants had tendency to be early-onset (mean age [range] at diagnosis, 52[43-67] versus 64[37-80] years, P = 0.001). PSA level at initial diagnosis and self-reported family history did not have significant difference between deleterious mutation carriers and non-carriers (P = 0.396 for PSA level, P = 0.753 for family history). Moreover, metastasis and Gleason score were not associated with deleterious germline variants. Conclusions: Our data showed approximately 52% DDR mutation occurred in other DNA repair pathways besides HRR and MMR, which was a unique spectrum of germline variants in Chinese prostate cancer patients. This indicated distinct genetic etiology and potential therapeutic targets of prostate cancer in Chinese population. Moreover, early-onset in patients with deleterious germline variants is an important clinical character. Whole DDR pathway genes’ testing and counseling should be considered for application for young individuals.
A novel computational tool for copy number variation detection in targeted circulating tumor DNA.
Authors: Yu Jianing , Han Tiancheng , Lin Xiaojing , Song Xue , Xie Hongyu , He Ji , Chen Weizhi 
Published: May 2019

e13051 Background: Targeted sequencing of circulating tumor DNA (ctDNA) has been used in early tumor detection and guidance of clinical cancer treatment. Accurate somatic copy number variation (SCNV) estimation is useful for better decisions in clinics, but remain challenging due to low percentage of tumor-cell-released DNA in circulating blood, in addition to the low signal-noise ratio and usual lack of normal control. Methods: To overcome these challenges and call SCNV at gene level, we develop a novel bioinformatics tool ctCNV. After correction for GC content, target region length and read counts, genome local scores at the gene level (GCS) were calculated, using 30 normal blood samples as control. Statistically significant cutoffs were determined using control. Results: The new method has been benchmarked with other SCNV calling tools such as CNVkit, which have been developed mainly for whole exome sequencing instead of targeted DNAseq. The validation experiment involves 6 mixed samples consisting of different proportions of known cell lines and real blood samples. ROC curve obtained through comparing the SCNV calling results with Droplet Digital PCR results show improvement of our method comparing to existing methods. Conclusions: As a summary, our study has three main results/contributions. First, we developed a novel computational tool for SCNV calling in targeted sequencing of ctDNA, with good sensitivity and specificity. Second, we thoroughly evaluated the performance of current available CNV calling tools in targeted sequenced ctDNA. Third, the raw data generated from our six real samples of gradient mixture of different cell lines and human’s samples can serve as an evaluation standard to other further computational tools for CNV calling in targeted sequenced ctDNA.
Radiomics analysis for pathological classification prediction in BI-RADS category 4 mammographic calcifications.
Authors: Lei Chu-qian , Wei Wei , Liu Zhen-yu , Xiong Qian-Qian , Yang Ci-Qiu , Zhu Teng , Zhang Liu-Lu , Yang Mei , Tian Jie , Wang Kun 
Published: May 2019

e13055 Background: To establish and validate a radiomics-based imaging diagnostic model to predict Breast Imaging Reporting and Data System (BI-RADS) category 4 calcification of breast with mammographic images before biopsy and assess its value. Methods: A total of 212 BI-RADS category 4 pathology-proven mammographic calcifications without obvious mass on mammography were retrospectively enrolled (159 in primary cohort and 53 in validation cohort). All patients received ultrasound inspection and the results were available. 8286 radiomic features were extracted from each mammography images. We utilized machine learning to build a radiomic signature based on optimal features. Independent clinical factors were selected by multivariable logistic regression analysis, and we incorporated the radiomic signatures and risk clinical factors to build a radiomic nomogram. The performance of the radiomic nomogram were assessed by the area under the receiver-operating characteristic curve (AUC). Results: Six features were selected to develop the radiomic signatures based on the primary cohort. Combining with menopausal states, the individualized radiomic nomogram reached an AUC of 0.803 in the validation cohorts, and its clinical utility was confirmed by the decision curve analysis. The difference was significant between the AUC value of differentiating results of the radiomic nomogram compared with ultrasound, mammography and combined modality respectively(p < 0.05 in all three groups). Especially, for patients with MG+/US- calcifications, radiomics nomogram can be screen out benign calcifications. Conclusions: Based on mammographic radiomics, we developed a method for prediction of pathological classification in BI-RADS IV calcification, which has a certain predictive effect.
A non-interventional, multicenter study to assess prevalence of BRCA1 and BRCA2 mutation among ovarian, primary peritoneal, and fallopian tube cancer patients in India.
Authors: Kodagali Rohit , Gupta Sudeep , Rajappa Senthill J , Advani Suresh Hariram , Agarwal Amit , Aggarwal Shyam , Goswami Chanchal , Dattatreya Palanki Satya , Arya Devavrat , Patil Shekhar 
Published: May 2019

e13073 Background: BRCA1 and BRCA2 are tumour suppressor genes.1,2 Functional BRCA proteins regulate cell growth and prevent abnormal cell division that might lead to tumour development. Approximately 17% (Range 3 – 27 %) of ovarian cancer patients worldwide have a BRCA mutation.3 This study aimed to estimate the prevalence of germline BRCA mutations among previously and newly diagnosed ovarian, primary peritoneal or fallopian tube cancer patients in India. Methods: This is a non-interventional, cross-sectional, multicenter, prospective, observational study conducted at 15 sites from different geographical regions across India. The study targets to enroll 240 patients over 6 months. The calculated sample size for this study is 228, assuming 5 % precision and a dropout rate of 10 %. The study enrolled females with new or previous diagnosis of ovarian, primary peritoneal, or fallopian tube cancer. No study medication was administered as a part of study procedure. Results: In the interim analysis performed on the first 100 enrolled patients, 22% of Ovarian, primary peritoneal or fallopian tube cancer patients were found to be BRCA1/BRCA2 mutation positive (CI 0.1433-0.3139). 52% of these enrolled patients were found to have serous histopathology, 23.1% of which were found to be BRCA1/2 positive. The percentage of BRCA1/2 mutation status in patients who had a family history of ovarian or breast cancer was found to be 66.7% and 62.5% respectively. Conclusions: In this study, the prevalence of BRCA1 and BRCA2 mutations among patients with ovarian, primary peritoneal and fallopian tube cancer patients in the first 100 patients enrolled was found to be 22%. References: 1. Vos S, et al. Crit Rev Oncol Hematol. 2018 Jul;127:29-41; 2. Solodskikh SA et al. Mutat Res. 2019 Jan;813:51-57; 3. Alsop K, et al. J Clin Oncol. 2012;30(21):2655-2663.
Utilizing social media for cancer prevention.
Authors: Lopez Ana Maria , Morales Jennyffer , Harding Garrett , Branson Donna 
Published: May 2019

e13076 Background: Cancer prevention and cancer screening behaviors are challenging to support. A myriad of variables including improved knowledge, language access, and health care access serve as facilitators for cancer screening behaviors. Utah is a vast state that is remarkably sparsely populated with more than 96% of the state defined as either rural (< 100 persons per square mile) or frontier (< 7 persons per square mile). Huntsman Cancer Institute is the only academic health center in the Mountain West and serves as the only NCI Comprehensive Cancer Center in the region. Methods: Access to the internet and to social media helps to bridge geography and support engagement. Facebook Live and Twitter Chats were used to deliver content. Language, Spanish, access was considered. Social media was also utilized to connect interested populations with in-person cancer prevention education events. Results: We will present our outreach results by intervention. Conclusions: Our work has successfully engaged rural and Latino populations in cancer prevention activities through social media.
Temporal trend of microbiological profiles among patients with bloodstream infections: A comparison between cancer and noncancer patients in a nationwide database.
Authors: Hsieh Ronan Wenhan , Schrank Gregory M , Hsu Wan-Ting , Su Ke-Ying , Lee Chien-Chang 
Published: May 2019

e13078 Background: Bloodstream infection (BSI) is a leading cause of in-hospital mortality for cancer patients. Our goal is to describe the temporal trend of microbiological profiles and inpatient outcomes through a large national database. Methods: National Inpatient Sample is the largest U.S. database of hospitalized patients including 20% of patients from 4,378 hospitals. Hospitalizations of patients with BSI were identified by ICD-9 codes for bacteremia and fungemia from 2006-2014. 21 common microorganisms were identified by ICD-9-CM codes as the cause of BSI. We assessed the trend of incidence and mortality by linear regression and compared the in-hospital mortality between cancer and noncancer BSI patients by propensity score adjusted Cox proportional hazard model. Results: A total of 13,996,374 patients with BSI were identified (cancer 13.6%, noncancer 86.4%). Among cancer patients, gram positive bacteria (GPB) are the leading pathogens (27.38%), followed by gram negative bacteria (GNB) (23.59%), fungus (4.81%) and anaerobe (1.21%). Anaerobe had the fastest annual increase rate of incidence (16.54%), followed by GNB (15.77%), fungus (11.61%) and GPB (7.41%). Cancer patients had a faster increase rate of incidence than noncancer patients. The in-hospital mortality was highest for anaerobe (16.14%), followed by fungus (15.71%), GPB (13.65%) and GNB (12.14%). Except for fungal BSI, the mortality for other types of BSI decreased significantly. GNB had the most annual mortality decrease (-2.51%), followed by GPB (-2.48%) and anaerobe (-1.47%). Cancer patients had higher in-hospital mortality than noncancer patients (PS-matched HR 1.25, 95%CI: 1.24, 1.26), especially in GNB BSI (PS-matched HR 1.29, 95%CI: 1.27, 1.31). Using breast cancer patients as reference, lung cancer BSI patients had the worst relative mortality risk (1.65, 95%CI: 1.60, 1.69). Conclusions: The incidence of BSI increased steadily among cancer patients from 2006-2014, with GNB BSI increasing at the highest rate. Except for fungus, mortality of GNB, GPB and anaerobe decreased continually. Compared with noncancer patients, cancer patients had a larger increase in the incidence of all types of BSI, especially anaerobes, and higher mortality than noncancer patients. BSI in lung cancer patients was associated with the highest mortality rate.
Disparities in HER2 testing in breast cancer.
Authors: Paryani Vijay , Schroeder Mary Chen , Klepin Heidi D. , Melin Susan Anitra , Russell Greg B. , Winkfield Karen Marie , Thomas Alexandra 
Published: May 2019

e13084 Background: Although targeted therapies directed at human epidermal growth factor-2 (HER2) impact breast cancer outcomes, studies have found geographic variation in testing rates. We report population-based patterns of HER2 testing by patient, tumor and geographic characteristics. Methods: Retrospective analysis of Surveillance, Epidemiology, and End Results (SEER) data included women diagnosed 2010-2015 with de novo breast cancer. Women were categorized by age, race, stage, year of diagnosis, and receipt of estrogen receptor (ER), progesterone receptor (PR), and HER2 testing. SEER classified lack of testing with “test ordered, results not in chart” and “test not done.” We report on cases with HER2 “test not done”. Records missing any variables were excluded. County-level measures of socioeconomic status were included for each woman. Univariate and multivariate logistic regressions identified factors associated with testing. Results: Of 281,214 new breast cancer diagnoses, 1.75% had HER2 “test not done”. ER and PR testing were “not done” in 0.57% and 0.74% of cases, respectively. HER2-testing rates improved over time: 2.54% not tested in 2010 and 1.30% in 2015 (p < 0.01). The following characteristics were associated with higher rates of “test not done”: age >70 vs < 50 (OR = 1.33, p < 0.01), blacks vs whites (OR = 1.23, p < 0.01), Stage IV vs I (OR = 2.27, p < 0.01). Regional variation was also seen, with registries reporting HER2 “test not done” ranging from 0.18%-2.89%. On multivariate analysis (Table), HER2 testing was less likely for women age ≥ 70, blacks, Stage IV disease, and those living in counties with high rates of less than high school education. Conclusions: Rates of HER2 testing have increased. However, disparities exist and are associated with age, race, stage, geography, and education. Understanding the cause of these disparities could ultimately enhance access to appropriate therapy and improve disease outcomes. Odds of not having HER2 testing (select results from multivariate analysis). [Table: see text]