bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging techniques in pancreatic cancer screening: Preliminary results from the PanGen-FAM registry.
Authors: Guillen-Ponce Carmen , Mocci Evelina , Earl Julie , Marquez Mirari , Milne Roger , Molina-Garrido MJ , Guerrero Carmen T , Real Francisco X , Malats Nuria , Carrato Alfredo 
Published: March 2020

1529 Background: The incidence of pancreatic cancer (PC) is low, thus screening is recommended for individuals considered to be at high risk. These include members of families with ≥ 2 relatives with PC (FPC), Peutz Jegher syndrome, hereditary breast/ovarian cancer (HBOC), familial atypical multiple mole melanoma and Lynch syndrome. Previous studies have shown that non-invasive precursor lesions, such as intraductal papillary mucinous neoplasm (IPMN) and pancreatic intraepithelial neoplasia (PanIN) are more common and of a higher invasive grade in patients with a family history of PC. Methods: Baseline screening consisted of endoscopic ultrasound (EUS) and computed tomography (CT) and magnetic resonance imaging (MRI). FNA-EUS was performed when mass lesions or cysts ≥1 cm in size were encountered. The possibility of surgical intervention or ongoing clinical observation was discussed by a multidisciplinary team in the case of abnormal findings. Furthermore Circulating Tumor Cells (CTC) in peripheral blood as a diagnostic marker was assessed. Thirty-five individuals from FPC and HBOC families were screened between October 2011and December 2012. Results: The most frequent abnormal findings by EUS were parenchymal changes found in chronic pancreatitis (hyperechoic foci, echogenic strands, lobularity, cysts). Overall 13 (41%) patients showed at least 1 of these changes; of note, 7 patients were from the same FPC family. Four patients were diagnosed with cystic lesions by EUS; two lesions were confirmed by MRI but not by CT, one lesion was confirmed by both MRI and CT and was compatible with a mucinous tumor < 1cm in diameter and one lesion was detected only by EUS. One patient with cystic lesion >1 cm in size underwent EUS-FNA and the cytology showed benign celularity. One patient has a solid lesion, and it was a neuroendocrine tumor. The remaining patients with cystic lesions were proposed for ongoing close clinical observation. CTC have not been detected in 54 patients tested. Conclusions: A high prevalence of pancreatic abnormalities was found in patients from FPC families. Preliminary data suggest that EUS is the most sensitive method to detect small tumors and premalignant lesions.
Prevalence and differentiation of hereditary breast and ovarian cancer in Japan.
Authors: Nakamura Seigo , Iwase Takuji , Nishimura Seiichiro , Yamauchi Hideko , Nomizu Tadashi , Ohsumi Shozo , Takahashi Masato , Baba Shinichi , Shimizu Tadao 
Published: March 2020

1534 Background: Breast cancer is the most common female cancer, according to the Center for Cancer Control and Information Service in Japan. However, the lifetime breast cancer risk in Japan is markedly lower (one in 16) than in the U.S. or Europe. We assembled needed data on the prevalence and characteristics of BRCA1/2 in Japan. Methods: Our study of BRCA 1 and 2 (BRCA1/2) collected data at 8 institutions in Japan on 320 individuals with a strong family history of breast cancer, according to the NCCN guidelines, by the end of March, 2012. Results: Among 260 proband cases, 46 (17.7%) were positive for BRCA1 and 35 (13.5%) were BRCA2 positive. Therefore, the total pathological mutation rate was 30.7%. Pathology data after breast surgery were obtained from 35 cases of BRCA1 mutation, 22 (62.9%) of which were triple negative and 10 (29.4%) were Luminal type. On the other hand, 24 cases (85.7%) of BRCA2 mutations were Luminal type. The most prevalent BRCA1 mutation site was L63X, found in 10 families. L63X was reported previously by studies in Japan, and it may be a founder mutation. We found 2 cases of large deletion detected by MLPA, comprising the first two reported cases in Japan. One was an entire deletion of exon 20 and the lacked exons 1-9. Eight cases of BRCA1 (3.1%) and 12 (4.6%) BRCA2 were uncertain variants. TN with a family history ovarian cancer were 14/20 (70%), TN under 40 y/o 17/23 (73.9%) and TN with one or more breast cancers in family history 19/32 (59.4%) showed higher incidences of BRCA1/2, especially BRCA1. Conclusions: HBOC may have nearly the same prevalence in Japan as in the U.S. or Europe. If TN cases are taken into account, the ratio of BRCA1 is higher. L63X may be one of the founder mutations in Japan. A nationwide database of HBOC is important to address these challenges: (1) To develop risk models for BRCA1/2 carriers in Japan (2) To identify the proper methods to detect cancer occurrence among Japanese BRCA1/2 carrier early (3) To differentiate whether uncertain mutation variants found in Japan are deleterious.
Timing of referral to genetic counseling among women with gynecologic or breast cancer.
Authors: Bregar Amy J , Febbraro Terri , Robison Katina , Scalia Wilbur Jennifer , Kent Laprise Jessica , Lopes Vrishali , Legare Robert Duffy , Stuckey Ashley 
Published: March 2020

1545 Background: The National Comprehensive Cancer Network (NCCN) has established guidelines delineating appropriate candidates for genetic counseling. While genetic predisposition is responsible for a small percentage of cancer, genetic referral at diagnosis may effect treatment decisions. We aim to determine factors associated with timing of referral in women with breast and gynecologic cancers. Methods: Patients from an academic women’s oncology program were identified who met a subset of NCCN referral criteria for genetic evaluation between 2004-2010 (ovarian cancer at any age, breast cancer ≤ 50 years of age, or uterine cancer < 50 years of age). A retrospective chart review was conducted. Statistics were analyzed using SAS v. 9.2 (SAS Institute, Cary, NC); categorical variables were compared by chi-square or Fisher's exact test and continuous variables were compared by ANOVA. The study was approved by the hospital Institutional Review Board. Results: 820 women with cancer (26% uterine, 38% breast, 35% ovarian) were included. The overall referral rate was 22%; more breast than gynecologic cancer patients were referred (34% vs. 28%, p<0.0001). Breast cancer patients were more often referred at diagnosis compared to women with uterine (p<0.0001) and ovarian cancer (p=0.007). Early stage breast cancer patients were more often referred at diagnosis compared to women with late stages (p=0.03). Among ovarian cancer patients, those with late stages were more often referred at diagnosis compared to women with early stages (p=0.02). Age at diagnosis, family history, and parity were not associated with timing of referral. Among women with breast cancer, 26% of referred patients had a prophylactic contralateral mastectomy compared to 8% of those not referred (p<0.0001). Conclusions: Genetic counseling is underutilized in breast and gynecologic malignancies. The timing of referral varies widely and genetic counseling may impact treatment decisions. Breast cancer diagnosis, early stage breast cancer, and late stage ovarian cancer are associated with earlier referral for genetic evaluation. Further research is needed to determine additional factors that may increase referral rates and impact timing of referral.
Transcriptional regulation and prostate cancer risk loci.
Authors: Klein Robert J. , Xu Xing , Hussain Wasay , Farber James , Vaananen Riina-Minna , Taimen Pekka , Vijai Joseph , Hayes James E. , Lilja Hans , Pettersson Kim , Rubin Mark A. , Demichelis Francesca , Offit Kenneth 
Published: March 2020

1554 Background: While genome-wide association studies (GWAS) have identified numerous loci at which common single nucleotide polymorphisms (SNPs) are clearly associated with the risk of developing prostate cancer, the mechanism by which these variants influence disease is not clear. Based on the observation that regions of the genome with marks of transcriptional regulatory elements harbor SNPs that are more likely to be under negative selective pressure, we hypothesized that many prostate cancer associated SNPs, or their correlated proxies in linkage disequilibrium, function by altering regulation of nearby genes through alteration of transcription factor binding sites. Two predictions of this hypothesis are that there will be an enrichment of prostate cancer risk SNPs or their proxies in regulatory elements in prostate tissue and that some of these SNPs will correlate with the expression levels of nearby genes. Methods: To test the first prediction, we compared the number of prostate cancer risk SNPs (or their proxies) that overlap with DNase hypersensitive sites in the LNCaP prostate cancer cell line with randomly selected SNPs matched for allele frequency, distance from nearby genes, and local gene density. To test the second prediction, we asked if any of the known prostate cancer risk SNPs are associated with mRNA expression levels of nearby genes. Results: We found a four-fold enrichment of real prostate cancer risk SNPs overlapping with DNase hypersensitive sites versus the random set (p=0.03) at an r2 threshold of 0.95. In both tumor and benign prostate tissue, we found that a recently identified prostate cancer risk SNP is associated with expression levels of IRX4, a transcription factor previously implicated only in cardiac development. Conclusions: These data support the hypothesis that many GWAS-identified risk SNPs alter transcriptional regulation of nearby genes.
Assessing breast cancer risk in primary care: What can we learn from cardiovascular disease?
Authors: Phillips Kelly-Anne , Keogh Louise A. , Steel Emma , Collins Ian M. , Emery Jon , Pirotta Marie , Mann Bruce , Butow Phyllis , Trainer Alison , Moreton Jane , Antoniou Antonis C. , Cuzick Jack M. , Hopper John L. 
Published: March 2020

1559 Background: Routine assessment of breast cancer (BC) risk by primary care clinicians (PCCs) might improve uptake of BC prevention and screening interventions, thus reducing morbidity and mortality as has occurred for cardiovascular (CV) disease. Methods: Australian PCCs were recruited through local professional networks. Facilitated focus group discussions about current practice of assessing and managing BC risk were audiotaped, transcribed verbatim and managed using QSR NVivo qualitative data management software. A coding framework was developed based on the transcripts, data were coded and each code further analyzed to identify key themes. Results: 17 PCCs (12 doctors, 5 practice nurses) participated in 2 focus groups. 41% were male, median age 49 years, median number of years in practice was 15. Approaches to assessment and management of BC risk differed markedly from that of CV risk. PCCs see assessment and management of CV risk as an intrinsic, expected part of their role. Practice software prompts trigger CV risk assessment and PCCs often use an online tool (www.knowyournumbers.co.nz) to provide personalized risk estimates and to discuss management options for CV risk. Conversely, assessment of BC risk is not routine or prompted by practice software, is generally patient (not clinician) initiated, and management, beyond routine BC screening (e.g. chemoprevention), is considered outside the PCCs domain. Most PCCs are not familiar with, or using, BC risk assessment tools. PCCs suggested they could potentially routinely assess and manage BC risk. Such an approach would need to be widely endorsed as within the remit of primary care and would be enhanced by an online tool that is accessible, quick, visual (graphs and pictograms), evidence-based and regularly updated. Ideally, its use would be prompted by their practice software. Conclusions: There is a clear opportunity in primary care to enhance the capacity and motivation of clinicians to assess and manage BC risk. A risk assessment and decision aid tool, integrated into primary care software, might facilitate routine appropriate management of BC risk in the Australian primary care setting, modelling what has already been achieved for CV disease.
Risk-adapted screening in bladder cancer with the open-access tool RiskCheck Bladder Cancer: Proof of principle by the health service research foundation IQUO.
Authors: Geiges Goetz , Koenig Frank , Lüdecke Gerson ,   Interessensverband zur Qualitätssicherung der Arbeit niedergelassener Uro-Onkologen in Deutschland e.V. (IQUO)
Published: March 2020

1571 Background: The open-access questionnaire RiskCheck Bladder Cancer (RCBC) was proven in daily routine work from German urologists organized in the health services research foundation IQUO on asymptomatic patients to identify BC risk exposure and its relation to detectable tumors. Methods: The open-access RCBC questionnaire checked asymptomatic patients for their BC risk exposure in relation to personal-, smoking-, occupation- and medical induced risk. This resulted in a risk stratification with low- intermediate- and high risk. The intermediate and high risk subjects were checked for tumor presence by routine diagnostics. IBM-SPSS 20 was used for descriptive statistics and effectiveness was proven by classification tree analysis and cross-table analysis with Chi-square test. Results: Out of 303 checked asymptomatic persons 274 (90.4%) were negative for tumor and 29 (9.6%) had a detectable tumor. In the group of NED 176 (68.1%) persons were classified as low risk, and 98 (16.2%) with tumor risk. Out of the 29 detected tumors 20 were at intermediate or high risk (68.9%). This resulted in an over all detection rate of 6.6% and focused on the risk population of 16.9%. The RCBC risk assessment was significant (p < 0.01). Sensitivity 69.0%, specificity 64.2%, NPV 95.1%, PPV 16.9%, false positive cases 35.8%, false negative cases 31.0%, accuracy 64.7%. Compared to the common incidence (35/100,000) this is an increase in effectiveness of 188.6 in the screened population and 482.8 in relation to the risk population alone. Conclusions: Preventive medical care becomes effective because RCBC is able to condense a population with focusing investigations on people living under risk. A reasonable preventive care by a yearly recall control in urological offices for the risk population (32.3%) can be organized. In consequence the assessment is work effective, aim achieving and in result cost effective. The questionnaire RCBC integrates evidence based bladder cancer inductors, is easy in use and as a open-access tool available in 10 languages via internet to all medical services. www.riskcheck-bladder-cancer.info.
Effects of obesity and smoking on survival in non-small cell lung cancer.
Authors: Hansra Damien Mikael , Koru-Sengul Tulay , Zhao Wei , Miao Feng , Tannenbaum Stacey , Monedero Alicia P , Lee David J , Byrne Margaret M , Hurley Judith 
Published: March 2020

1586 Background: Tobacco is the leading cause of preventable death in the US and is linked to many cancers most notably lung cancer. It is established that smoking not only causes lung cancer but is also associated with decreased survival. Obesity is an emerging leading cause of morbidity and mortality in the US and the relationship between obesity, tobacco, and survival in NSCLC is unclear. Methods: Data (n= 87,631) were obtained from linkage of the 1996-2007 Florida Cancer Data System, a population-based cancer registry, to the Agency for Health Care Administration database providing procedure and diagnoses codes. Survival time was calculated from date of diagnosis to date of death. Smoking status was categorized as never, current, and former. Obesity (yes/no) was determined by body mass index greater than 30. Cox proportional regression models were used to predict survival; demographic, clinical, treatment factors, and comorbidities were included in adjusted models with smoking status and obesity as the main factors. Results: The majority of patients were either former (49%) or current (40%) smokers, and non-obese (93%). There were significant differences between survival curves and median survival (months) for obese vs. non-obese patients (19.9 vs.9.8; P<.001). Former and current smokers had shorter median survival than never smokers (10.8 & 9.2 vs. 11.9; P<.001). Survival rates (%) at 1-yr (60.0 vs. 44.8; P<.001), 3-yr (38.4 vs. 22.1; P<.001) and 5-yr (30.2 vs. 15.0; P<.001) were better for obese vs. non-obese patients. Independent predictor of worse survival in the unadjusted model was former (HR 1.08; P<.001) and current (HR 1.20; P<.001) smokers compared to never. Obese patients had better survival vs. non-obese patients (HR 0.64; P<.001). In the adjusted model, controlling for extensive variables and comorbidities, former (HR 1.14; P<.001) and current (HR 1.22; P<.001) smokers still had significantly worse survival vs. never smokers. Obese patients still had better survival (HR 0.84; P<.001) vs. non-obese patients. Conclusions: Our results show that being a former or current smoker worsens survival while obesity improved survival regardless of smoking status when compared with non obese patients.
Correlation between anthropometric, pathologic data, and 21-gene recurrence score assay in early-stage breast cancer.
Authors: Quintyne Keith Ian , Woulfe Bernie , Coate Linda , Gupta Rajnish K. 
Published: March 2020

1591 Background: Obesity or body mass index (BMI) > 30kg/m2 is a grave public health concern. Poorer outcome has been documented in obese breast cancer patients. We report the use of the Oncotype Dx Recurrence Score (RS) assay and its correlation with BMI and pathologic data. Methods: Study period: 01/09/08 – 31/05/12. Data was derived from: MWCC database; pathology reports; patient files; RS reports. Statistical analysis was carried out using R. Results: 89 patients were found. Median follow-up: 21.4 months. See Table for data. Conclusions: For this cohort: A skewed pattern in RS assay scores was observed in obese patients, where there were more intermediate and high scores, although this was not significant in multivariate model; tumour size and grade were shown to correlate with the RS assay results; these findings are thought-provoking and certainly can augment to the accruing energy balance data that has been increasingly of interest in oncological research. [Table: see text]
Effect of visual inspection with acetic acid (VIA) screening by primary health workers on cervical cancer mortality: A cluster randomized controlled trial in Mumbai, India.
Authors: Shastri Surendra Srinivas , Mittra Indraneel , Mishra Gauravi , Gupta Subhadra , Dikshit Rajesh , Badwe Rajendra A. 
Published: March 2020

2 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Sunday, June, 2, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Tumor pharmacokinetics (PK) and pharmacodynamics (PD) of SAR245409 (XL765) and SAR245408 (XL147) administered as single agents to patients with recurrent glioblastoma (GBM): An Ivy Foundation early-phase clinical trials consortium study.
Authors: Cloughesy Timothy Francis , Mischel Paul S. , Omuro Antonio Marcilio Padula , Prados Michael , Wen Patrick Y. , Wu Bin , Rockich Kevin , Xu Yi , Lager Joanne J. , Mellinghoff Ingo K. 
Published: March 2020

2012 Background: XL765 is a potent pan PI3K inhibitor with activity against mTOR and XL147 is a potent pan-PI3K inhibitor. Inhibition of the PI3K/mTOR pathway may be beneficial in the treatment of GBM. Methods: Patients with GBM who were candidates for a surgical resection were eligible for this exploratory study. Cohorts of 6-10 patients were treated with one of three regimens: Cohort 1: XL765 50mg twice daily (BID), Cohort 2: XL147 200mg once daily (QD), Cohort 3: XL765 90mg QD for >10 days prior to undergoing tumor resection. Tumor tissue was obtained at ~12, 24 and 3 hours after the last dose, respectively. Frozen tumor tissue and blood were analyzed for drug concentration (PK) and pathway modulation was analyzed in post-dose frozen tumor tissue and compared to reference tumor samples from GBM patients not treated with XL765 or XL147. Pharmacodynamic impact (PD) on the pathway, apoptosis and proliferation was examined by immunohistochemistry (IHC) in an FFPE tumor sample from each patient and compared to an archived tumor sample from an earlier surgery. Results: Enrollment is complete with 21 patients enrolled; 6, 6 and 7 were evaluable for the PK/PD analysis in cohorts 1, 2 and 3, respectively. The toxicity profiles for both drugs were consistent with previous studies. PK analyses revealed a mean tumor to plasma ratio of 0.38 and 0.40 in cohorts 1 and 3 and 0.27 in cohort 2. PD analysis by IHC revealed reduction compared to archived tumor in pS6K1 in 4/6 and 7/7 patients in cohorts 1 and 3 and 6/6 patients in cohort 2. Reduction in Ki67 was observed in 6/6 and 5/7 patients in cohorts 1 and 3 and 4/6 patients in cohort 2. Conclusions: XL765 when given on a QD or BID schedule to patients with glioma yields moderately higher distribution of XL765 into CNS tumor compared to XL147 based on tumor to plasma ratios. Decreases in pS6K1, consistent with pathway inhibition, and decreases in Ki67, consistent with inhibition of proliferation, were observed following treatment with both XL147 and XL765. Clinical trial information: NCT01240460.
Phase II trial of the phosphatidyinositol-3 kinase (PI3K) inhibitor BKM120 in recurrent glioblastoma (GBM).
Authors: Wen Patrick Y. , Yung W. K. Alfred , Mellinghoff Ingo K. , Lamborn Kathleen , Ramkissoon Shakti , Cloughesy Timothy Francis , Rinne Mikael , Omuro Antonio Marcilio Padula , DeAngelis Lisa Marie , Gilbert Mark R. , Chi Andrew S. , Batchelor Tracy , Colman Howard , Chang Susan Marina , Massacesi Cristian , DiTomaso Emmanuelle , Prados Michael , Reardon David A. , Ligon Keith L. 
Published: March 2020

2015 Background: The PI3K pathway is activated in most GBMs and represents a potential therapeutic target. BKM120 is an oral, pan-Class I PI3K inhibitor that enters the brain at therapeutic concentrations demonstrated to inhibit PI3K pathway, and potently inhibits the growth of U87 GBM tumors and human glioma tumor spheres in vitro and in vivo. Methods: The Ivy Foundation Early Phase Clinical Trials Consortium is conducting a phase II study of BKM120 in recurrent GBM patients with activation of the PI3K pathway (mutation, homozygous deletion or loss of IHC of PTEN, PIK3CA or PIK3RI mutations, or detectable pAKT). Additional eligibility criteria included radiologic progression, 1st or 2nd relapse, > 18 yrs, KPS > 60, adequate bone marrow and organ function, controlled blood glucose, and no enzyme-inducing antiepileptic drugs. Patients received BKM120 100mg daily. The study consisted of 2 parts conducted concurrently. Part 1 involved up to 15 patients who received BKM120 daily for 8-12 days prior to surgery for recurrent disease. Patients underwent FDG PET, pharmacokinetic (PK) studies, and tumor was obtained for drug concentrations and pharmacodynamic effects. Part 2 consisted of up to 50 patients with unresectable GBM treated with BKM120. The primary endpoint for Part 2 was 6-month progression-free survival (p0 =15%; p1= 32%). Results: To date 7 patients have been enrolled into Part 1, 33 into part 2. There were 5 women and 35 men. Median age was 54 yrs (29-68). Treatment was fairly well-tolerated. Major grades 3/4 toxicities were asymptomatic lipase elevation (5), fatigue (3), hyperglycemia (3), rash (3) elevated AST (1), and depression (1). Analysis of tumor from Part 1 showed reduction of pAkt by IHC. Genotyping of tumor specimens is ongoing. To date 33 patients had positive pAkt, 21 had PTEN loss by IHC. Of the first 19 patients who underwent whole exome sequencing, 3 had PIK3Ca mutations and 6 had PTEN mutations. Conclusions: BKM120 is generally well tolerated in patients with recurrent GBM and achieves adequate tumor concentration to inhibit pAkt. Updated PK and efficacy data and correlation of the latter with tumor genotype will be presented. Clinical trial information: NCT01339052.