bluuebunny/crossref_metadata_2025 huggingface dataset:
Histological growth pattern as a potential prognostic factor in patients operated for breast cancer liver metastases.
Authors: Bohlok Ali , Botzenhart Lara , Lucidi Valerio , Noel Jean Christophe , Demetter Pieter , Larsimont Denis , Donckier Vincent , Vermeulen Peter B.
Published: May 2019

e12576

Background: Indications for surgery in patients with breast cancer liver metastases (BCLM) remain ill-defined. Recently, the histological growth pattern (HGP), such as desmoplastic (dHGP), associated with angiogenesis and inflammation, or replacement (rHGP), associated with vessel co-option and in the absence of immune infiltrate, has been demonstrated as a significant prognostic factor in patients operated for colorectal liver metastases. In BCLM, the distribution and the prognostic value of HGP are poorly documented. We aimed to characterize HGP in a series of patients undergoing liver resection for BCLM and correlate these patterns with postoperative outcomes. Methods: A consecutive series of 58 patients undergoing liver resection for BCLM was reviewed. Clinicopathologic parameters of these patients were analyzed. HGPs were assessed in archival H&E stained tissue sections, according to international consensus guidelines. The proportions of rHGP and dHGP were determined in each metastasis. In case of multiple metastases, mean HGP was calculated for each patient. Patients were categorized as pure (100% rHGP or dHGP) or dominant phenotype ( > 50% rHGP or dHGP, on the entire tumor/normal liver interface). All these factors were correlated with overall and disease-free survivals (OS and DFS). Results: After a mean follow-up of 81 months, 5-years OS and DFS in global population were 49.7% and 22.7%, respectively. No clinicopathologic preoperative factor was found to be predictive for OS or DFS. HGPs were analyzed in a first set of 21 patients. All patients showed some rHGP component. Of these, 11 were pure rHGP (52.4%), 4 dominant-rHGP (19%) and 6 dominant-dHGP (28.6%). Five-years postoperative OS and DFS were of 19.4 and 18.2% in pure rHGP, as compared with 64.8 and 33.3% in patients with some dHGP component (p = 0.089). Conclusions: rHGP appears as the main phenotype of BCLM. First analyzes suggest that surgery for BCLM with pure rHGP is associated with a worse oncological outcome as compared to BCLM with a dHGP component.
Low-dose metronomic chemotherapy (LDMC) as an efficient treatment option in metastatic breast cancer: Results of an exploratory case-control study.
Authors: Battista Marco Johannes , Schnatz Carola , Almstedt Katrin , Brenner Walburgis , Heimes Anne-Sophie , Nezi-Cahn Sandra , Schwab Roxana , Hasenburg Annette , Schmidt Marcus , Krajnak Slavomir
Published: May 2019

e12578

Background: There is a growing importance of low-dose metronomic chemotherapy (LDMC) in metastatic breast cancer (MBC). In this retrospective case-control-analysis we compared the efficacy of LDMC and conventional chemotherapy in MBC. Methods: Each LDMC patient receiving oral cyclophosphamide (CTX) (50 mg daily) and methotrexate (MTX) (2.5 mg every other day) was matched with two patients who received conventional chemotherapy. Age, number of chemotherapy lines and metastatic lesions as well as hormone receptor (HR) status were considered as matching criteria. Primary endpoint was disease control rate greater than 24 weeks (DCR). Secondary endpoints were DCR in subgroups (number of chemotherapy lines, number of different metastatic lesions and HR status), progression-free survival (PFS) and duration of response (DoR). Results: A total of 35 cases and 70 controls entered the study. 31% patients with LDMC and 26% patients with conventional chemotherapy showed DCR (p = 0.644). Among younger patients DCR was 41% in LDMC vs. 30% in the control group (p = 0.534). In addition, DCR was achieved in 35% vs. 27% patients with ≤ 2 chemotherapy lines (p = 0.560) and in 36% vs. 20% patients with ≤ 2 different metastatic lesions (p = 0.168), respectively. In the triple negative group 30% LDMC vs. 5% control patients showed DCR (p = 0.095). PFS was 12.0 vs. 13.5 weeks (p = 0.415), DoR was 26.5 vs. 20.5 weeks (p = 0.628), respectively. Conclusions: In this retrospective case-control study we demonstrated a similar efficacy of LDMC compared to conventional chemotherapy in the treatment of MBC. Moreover, no significant differences were found in the subgroups studied. Therefore, the concept of LDMC may also be a treatment option in both younger and non-heavily pre-treated MBC patients who do not need rapid remission.
Patterns of mutation enrichment in metastatic triple-negative breast cancer.
Authors: Saravia Cesar H. , Flores Claudio J. , Schwarz Luis Jesus , Bravo Leny , Zavaleta Jenny , Araujo Jhajaira M , Neciosup Silvia P. , Pinto Joseph A.
Published: May 2019

e12596

Background: Triple-Negative breast cancer (TNBC) is a group of heterogeneous tumors with aggressive biology. The purpose of this research was to evaluate enrichment patterns of genomic alterations in metastatic TNBC (mTNBC). Methods: We retrieved genomic data (mutations and copy number variation) from 550 primaries TNBC (pTNBC) from the projects METABRIC and TCGA and 58 mTNBC from the projects “Mutational Profile of Metastatic Breast Cancers” and “The metastatic Breast Cancer Project”. Differences in the proportions of mutations between primary vs. metastatic tumors were evaluated by the Chisquare test and the percentage of enrichment in mTNBC was estimated. Pvalues were adjusted for multiple testing with the Benjamini-Hochberg method with and a FDR < 0.05. In addition we conducted an analysis of the hallmarks of cancers enriched in mTNBC. Results: In total, mutations in eight genes were significantly enriched in mTNBC after correcting for multiple testing. These genes included TTN, HMCN1, RELN, PKHD1L1, DMD, FRAS1 and RYR3. In the other hand, only amplification of RPS6KB2 was enriched in mTNBC. Deletions were enriched more frequently in the genes TET1, RHOA, EPHA5, SET, KCNJ5, ABCG4, NKX3-1, SDHB, IGF2, BRCA1, among others. The hallmark of “genetic instability and mutation” was over represented while the hallmark “activating immune destruction” was the least represented between the enriched genetic alterations in mTNBC. Conclusions: Despite the study limitations, we identified that deletions are the aberrations more commonly enriched in mTNBC while some biological processes could be targetable in order to improve the therapeutic opportunities in TNBC.
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]
Incidence and characteristics of cancer-associated thrombosis in a racially diverse population: A population-based study.
Authors: Raskob Gary E. , Wendelboe Aaron M. , Heller John Grady , Ding Kai , Reyes Nimia L. , Abe Karon , Adamski Alys , Beckman Michele G. , Richardson Lisa Carolyn
Published: May 2019

e13088

Background: Venous thromboembolism (VTE) is a common complication in cancer patients, but contemporary data on the incidence and characteristics of cancer-associated VTE in different racial populations is limited. We sought to measure the incidence rate and characteristics of cancer-associated VTE in a racially diverse population. Methods: We performed a prospective, population–based cohort study of VTE in Oklahoma County, OK during April 1, 2012–March 31, 2014. Surveillance staff regularly visited all tertiary care and relevant outpatient facilities in the county and reviewed the text from all imaging results of chest computed tomography or magnetic resonance imaging, lung perfusion scans, and ultrasound of the extremities to identify cases of VTE. Data on patient characteristics were collected from the electronic medical record. VTE was considered cancer-associated if the patient had a history of cancer other than basal or squamous cell skin cancer. Cancer was defined as “active” if metastatic or diagnosed within 6 months prior to VTE. Associations and incidence were calculated using the chi-square test and Poisson regression, respectively. Results: Of 3,255 patients with ≥1 VTE event (deep-vein thrombosis and/or pulmonary embolism), 732 (23%) had a history of cancer, of whom 309 had active cancer. The types of cancer varied widely. The age-adjusted incidence of cancer-associated VTE was 648 per 100,000 adult population (age ≥ 18). Incidence increased with each decade of age. The racial/ethnic-specific incidence rates were as follows (each per 100,000): Whites non-hispanic (607), Blacks non-Hispanic (557), Native Americans (128), Asian/Pacific Islanders (113) and Hispanics (70). Risk factors for VTE among the 732 with cancer-associated VTE included previous VTE (19%), hospitalization (37%), surgery (33%), and central venous catheter (22%). Of those with a history of cancer ≥ 6 months previously, 32% had no other identifiable VTE risk factor. Conclusions: Cancer-associated VTE comprised about 20-25% of the total population burden of VTE. The incidence varied substantially by race/ethnicity. An appreciable proportion of those with a history of cancer ≥ 6 months previously subsequently developed VTE in the absence of other risk factors.
Prediction of attendance to the "60 days law" within the patient navigation program to breast cancer in Rio de Janeiro, Brazil.
Authors: Gioia Sandra , Krush Lindsay , San Miguel Sandra , Galdino Renata , Brigagao Lucia , Goss Paul
Published: May 2019

e13100

Background: An applied study was conducted on how the use of machine learning techniques can help in the process of identifying compliance with the "60 Day Law", which states that all patients with cancer within the public system must initiate the treatment within 60 days after the diagnosis of cancer. Within the Patient Navigation Program (PNP) for breast cancer in Rio de Janeiro, the study aims to: 1) identify barriers to compliance with the Law; 2) ensure that at least 70% of patients recruited with breast cancer initiate treatment within the mandatory 60-day period; and 3) to construct a model that accurately predicts whether or not a patient meets the period established in the Law. Methods: From August 2017 to May 2018, 105 patients aged 33-80 years (mean 59 years) were recruited for navigation. For the development of the statistical analysis, three learning models were used AdaBoost, Decision Tree and GaussianNB. Results: Patients presented 0-I (17%), II-III (78%) and IV (5%) staging. The main barriers to compliance with the Law were fear and fatalistic thoughts (99%), financial problems (79%), and uncoordinated health care (76%).The PNP had 100% patient satisfaction and in 52% of the cases it helped at the beginning of the treatment within the period established by law. The AdaBoost learning model had superior results in relation to accuracy and f-score (0.8889 and 0.8333, respectively). Conclusions: The PNP generated a positive experience in the public health system, because it is an intentional and proactive process of individual assistance through the health system, accessing services, and actively overcoming the barriers to quality care. The study did not reach the success rate of 70% compliance with the Law as intended (having reached 52%). However, the barriers that NP cannot overcome, such as the lack of human resources and medical supplies, have been reported to health authorities and hospital administrators. We identified 38 important attributes for compliance with the Law, which simplifies the information required for model learning. In the Brazilian context, the PNP may represent an opportunity to adequately implement existing legislation and, as such, would have great potential for integration into federal, state, and local health systems. Clinical trial information: 62728616.5.0000.5274.
Bringing patient navigation to primary health care in Rio de Janeiro: Pilot project in the Andaraí community.
Authors: Gioia Sandra , Torres Cristiane , Galdino Renata , Brigagao Lucia , Heringer Alessandra , Medeiros Marcelle , Krush Lindsay , Goss Paul E.
Published: May 2019

e13104

Background: This research project aims to study the increase of mammographic coverage rate with Patient Navigation Program (PNP) in a community of Rio de Janeiro. The general objective is to measure adherence to Ministry of Health’s recommendations for breast cancer screening with mammography, with the help of a patient navigator. Other objectives include: (1) establish the viability of the PNP in this context; 2) identify the barriers to mammography screening and; 3) ensure that at least 70% of women recruited between 50 and 69 years of age and asymptomatic update the biennial mammographic examination and annual clinical examination, increasing the mammographic coverage from 14% to at least 70% considered acceptable by the World Health Organization. Methods: From March to September 2018, women from the Andaraí Community were recruited in the Municipality of Rio de Janeiro. The follow-up was carried out by telephone, e-mail, and text messages. Of the 678 women (average age = 58), 12% of women refused to participate in the PNP for cultural reasons. Results: All 599 women participants reported barriers to obtaining breast health care with the number of barriers reported ranging from 1 to 6 barriers, (average = 3). The main barriers were system problems with health care programming (100%), financial problems (64%), communication concerns with the medical staff (58%), fear (44%), and social support (14%). We obtained 100% satisfaction with the PNP and exceeded our goal with 88% mammographic coverage rate. Conclusions: The PNP for breast cancer in the Andaraí Community has proven to be feasible in the context of local public health. The PNP promoted an increase in the mammographic coverage rate to 88%, assisted in the transmission of quality information, reduced the fear of mammography, and facilitated access to breast health care. Clinical trial information: 70832117.8.0000.5279.
Prevalence of targetable mutations in black patients with lung cancer: A systematic review and meta-analysis.
Authors: Paul Yonette , Iyer Sunil G , Tamariz Leonardo , Nemeth Zsuzsanna , Lopes Gilberto
Published: May 2019

e13105

Background: Although poorer outcomes of lung cancer in Blacks compared to other racial groups has been strongly linked to socio-economic factors, it is important to investigate whether lower prevalence of targetable mutations limit treatment options, thereby also contributing to worse outcomes. This study examines the prevalence of EGFR, ALK, ROS-1 and BRAF lung cancer mutations in Blacks compared to other races. Methods: We conducted a meta- analysis compliant with PRISMA guidelines. Searched databases included PubMed/MEDLINE, Cochrane CENTRAL, EMBASE, Google Scholar and clinicaltrials.gov. Publication bias was mitigated by searching clinicaltrials.gov for unpublished studies. Searches were run to 11/19/2018. Two rounds of screening were performed based on title and then abstract by two independent reviewers. For the purposes of this study we defined racial groups as Black, Asian, Hispanic, and White/Caucasian. We selected studies of lung cancer patients (any stage or type) where the prevalence of at least one mutation was reported in Blacks. We calculated the pooled prevalence of mutations by racial group using fixed effects, exact binomial distributions and Freeman-Turkey double arcsine transformation to stabilize the variances. Results: Prevalence % of mutations by race reported with 95% Confidence Interval in parentheses N = number of tests performed We included 20 studies which totaled 11,867 lung cancer patients. Each mutation tested on a tissue sample was considered an event, for a total of 15,306 events. EGFR was the most prevalent mutation in Blacks (6%). Compared to other races Blacks had the lowest prevalence of all four mutations. Conclusions: In the era of targeted therapy, outcomes for metastatic lung have improved significantly. Of concern, our results show that Blacks are disproportionately ineligible for these therapies due to lower prevalence of targetable mutations. More research is needed to evaluate the unique tumor characteristics and therapeutic strategies in this sub group of patients, in the hope of achieving better disease outcomes.[Table: see text]
Study of the expression of programmed death ligand 1 (PD-L1) on non-small cell lung cancers (NSCLCs) at Bach Mai Hospital, Vietnam.
Authors: TRANG NGO Thuy , Pham Van Tuyen , Doan Minh Khuy , Hoang Anh Tuan , Lu Long-Sheng
Published: May 2019

e13107

Background: Programmed death ligand 1 (PD-L1) expressions is a known predictor for anti-PD1 therapy outcomes. This study is the first study that describe the status of PD-L1 status on Vietnamese non-small cell lung cancers (NSLCs) patients. Methods: Patients who were diagnosed with advanced NSCLCs and PD-L1 testing from 14 Dec 2017 to 14 Dec 2018 at The Pathology Center, Bach Mai Hospital, Hanoi, Vietnam. Study team collected data of age, gender, histopathological types, biopsy sites and PD-L1 expressions. Qualified pathologists interpret levels of PD-L1 via immunohistochemical (IHC) assays Ventana PD-L1 (SP263) with archive formalin-fixed, paraffin-embedded (FFPE) NSCLCs tissues (primary lung tumor or metastases) on VENTANA BenchMark XT. Results: In total 166 patients, the majority were male (73.49%) with male/female ratio is 2.77. Age range from 29 to 85 with median age was 61 years old. The most common histopathological type was adenocarcinoma (n = 143, 86.14%). Other patients including 19 squamous cell carcinoma (11.45%) and 3 patients with “not otherwise specified” (NOS) tissues (2.41%). Overall 127/166 (76.51%) specimens were taken from lung tumors while 39 (23.49%) samples were from lymph node (10), pleura (20), liver (2), pericardia (2), brain (3) and bone (2). Rates of high expression (≥50%), expression (≥1% and ≤49%) and no expression (<1%) of PD-L1 were 26.51%, 31.32% and 42.17%, respectively. In multivariable regression analysis, we did not observe correlation between PD-L1 expression and age (p = 0.25, CI 95%), type of histopathological tissues (p = 0.41, CI 95%), biopsy sites (compare between lung vs non-lung samples, p = 0.89, CI 95%). Male gender has higher chance to have high expression ò PD-L1 with p = 0.0044, CI 95%. In female patients only, age has negative correlation with PD-L1 expression (p = 0.014, CI 95%). Conclusions: We found that male Vietnamese or younger female NSCLCs are likely to have higher PD-L1 expression. Further data on sequential anti PD-L1 treatment after PD-L1 testing is needed for validation the benefit of Ventana PD-L1 (SP263) IHC assay in Vietnamese NSCLC patients.
Effects on histologic subgroup, race, and BMI in 2,110 breast cancer patient: Results from single institution in Georgia.
Authors: Alvarez Ricardo H. , Rollins Rebecca , Ensor Joe , Nixon Daniel W. , Ramey Jonathan , Pannell Rachel , Rados Karen , Ahn Eugene R , Aithal Sramila , Lynch Cynthia , Pabbathi Haritha , Hansra Damien , McKnight John Edward , Kim Elizabeth MH , Johnson Anita
Published: May 2019

e13112

Background: Disparities in breast cancer (BC) care still clearly exist among Whites (W) and African-Americans (AA) racial groups. These disparities resulting in higher mortality among AA compared to W. The objective of this analysis was to estimate the prevalence of BC subtypes in a population-based sample of BC cases, collected in a Breast Cancer Database (BCD) and to examine correlations with demographic and clinicopathologic variables and patient survival. Methods: retrospective analysis of patients registered at BCD was performed. Pts with BC were analyzed for differences in survival based on histologic subgroup (HS), race and BMI. Median Kaplan Meyer estimate for potential follow-up was 13.1 months with 95% CI (10.6, 15.0). Univariate and multivariate analysis were used to identify factors associated with demographic and cancer biology variables. Results: A total of 2,110 patients were registered at BCD and were available for this analysis.The median age at diagnosis was 50.8 years with 95% CI of (50.2, 51.0). 50% were W and 46.6% were AA. HS were classified by immunohistochemistry CLIA central lab, ER+ 61.1%, HER2+ 21.8% and TNBC 17%.Fisher’s exact test showed statistically difference in HS distribution among the races (p < 0.0001); 25% and 11.7% TNBC, for AA and W, respectively. The mean BMI was 29.0 with 95% CI of (29.6, 30.2). BMI characteristics were obese 47.2%, overweight 28.6% and normal 22.2%. Fisher’s exact test showed statistically difference in BMI distribution among the races, 57% and 39% obesity, for AA and W, respectively (p < 0.0001). Log-rank test showed that 2-years OS is worse for TNBC (48%), than for ER+ (72%) and HER2+ (75%). In the multivariable model AA survival was statistically inferior than for W ( p= 0.0094). Cox proportional hazard model was constructed to assess the effect of age, BMI, race and HS (Table). Conclusions: This single institution analysis demonstrated a statistically differences between TNBC, AA, and abnormal BMI as poor prognostic factors in BC pts impacting OS. Further research should investigate how to improve care for AA women who are at higher risk for breast cancer mortality. [Table: see text]
The association between volumetric breast density and breast cancer subtypes among women newly diagnosed with breast cancer.
Authors: Balema Wintana A. , Moseley Tanya W. , Weaver Olena , Hess Kenneth R. , Brewster Abenaa M.
Published: May 2019

e13115

Background: Increased breast density is a strong risk factor for breast cancer, women with high breast density have a four to six-fold increased risk of breast cancer compared to those with low density. This study explores breast density as a risk factor for specific breast cancer subtypes in order to improve risk assessment and screening recommendations for the general population. Methods: 790 women ≥ 18 years with breast cancer were evaluated who had volumetric percent density and volumetric density grade (VDG) assessed from diagnostic mammograms obtained within 9 months of diagnosis. Breast cancer subtypes were approximated based on the estrogen receptor (ER), progesterone (PR) and Her2neu status; ER and/or PR positive/Her2 negative or positive (HR+), ER and PR negative and Her2 positive (Her2-positive) and ER, PR and Her2 negative (TN). A linear model on a log scale was conducted to evaluate the associations between percentage volumetric breast density and VDG and breast cancer subtypes and race. Results: 36% of women were < 50 years and 64% ≥50 years, 76% were white, 12% Black and 12% other race. There was no significant association between breast cancer subtype with age ( P = 0.068), BMI ( P = 0.81) or race ( P = 0.11). Women with VDG 1 or 2 were more likely to have HR+ (81.3%) than Her2-positive (5.1%) or TN subtypes (13.6%) (P = 0.024). There was no significant association between the percent volumetric breast density and breast tumor subtype or race. Conclusions: We found a significant association between lower breast density measured using VDG and the HR+ breast cancer subtype. This suggests a potential opportunity for assessing volumetric density grade for the development of individualized risk prediction models and for the identification of women who may benefit from preventive therapy to reduce HR+ breast cancer risk.
Adverse events following the use of immune checkpoint inhibitors: An analysis of the WHO VigiAccess database.
Authors: Nikita Nikita , Zinner Ralph , Johnson Jennifer Maria , Ghosh Natasha , Wilson Melissa , Lu-Yao Grace L.
Published: May 2019

e13118

Background: Immune checkpoint inhibitors (ICIs), especially ipilimumab (ipi) and nivolumab (nivo), have received approvals from the U.S. Food and Drug Administration for the treatment of multiple tumor types. These medications have shown great promise in the treatment of several malignancies but are associated with immune-related adverse events. This study was undertaken to better understand the patterns of adverse events following different ICIs. Methods: We used the World Health Organization (WHO) Vigiaccess Database, the largest adverse events reporting database, to identify, summarize, and report adverse drug events (AE) attributed to ipi and nivo. The database contains reports for ipi beginning in 2008 and for nivo beginning in 2012. We manually extracted the data from the database and conducted Chi-square tests to examine the difference in occurrence of AEs in various organ systems between patients receiving ipi and nivo. The five most common organ systems affected by AE associated with ipi and nivo were identified. Results: AEs were reported in 15,504 ipi users and 21,306 nivo users. Ipi users reported significantly higher AEs in gastrointestinal system compared to nivo users (p < 0.0001). Conversely, nivo users reported significantly higher AEs in respiratory disorders (p < 0.0001), skin and subcutaneous tissue organ systems (p = 0.0001), and neoplasms benign, malignant and unspecified (p < 0.0001) compared to ipi users. Conclusions: To our knowledge this is the largest study on reported AEs following ipi and nivo. The patterns of treatment-related AEs differed significantly for these two immune checkpoint inhibitor therapies. Further studies are required to guide treatment selection.[Table: see text]