bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic alterations in matching primary tumors and metastasis in breast cancer.
Authors: Jiang Tingting , Szekely Borbala , Szasz Attila Marcell , Kluger Yuval , Kulka Janina , Pusztai Lajos 
Published: March 2020

1549 Background: We examined DNA sequence alterations in matching normal tissues, primary breast cancers and metastatic lesions to study the genomic evolution of breast cancer. We also assessed technical reproducibility. Methods: DNA was extracted from formalin fixed paraffin embedded tissues obtained during autopsies from 3 patients including 12 specimens. We performed paired-end whole exome sequencing with SOliD V4 Genome Analyzer using the Agilent Sure Select All Exon Kit including technical replicates. Nucleotide variants (NV) were detected by Varscan V2.2 and functional impact was predicted by ANNOVAR. Results: After 4 QC steps (duplicate and strand bias removal, base quality and minor allele frequency filters) that removed 98.81% of variants per sample (range 96.50%-99.99%). We observed on average 2648 new NVs per cancer sample (range 10-5541) at a mean coverage of 72 (range 19-283) and mean library size of 48270660 base (range 7764034 base - 60752085 base). Concordance for high quality NVs reached 95% (range 92%-98%) in replicates. Mutation rate in the primary cancer differed from patient to patient (range 10.41per Mb to 18.29 per Mb) with more mutations seen in patients with longer disease history and extensive prior therapy. We also observed more differences in mutations between primary tumors and metastasis than expected by technical nose alone. On average, 234(83.53%) mutations were shared between a primary tumor and a metastasis (range 4 – 947; 62.5%-97.63%) and the number of site-specific mutations ranged from 0 to 251. An index for assessing mutational heterogeneity was greater in primary cancers compared to their metastasis. Mapping of variants with predicted functional impact yielded different targetable anomalies for different tumor sites. Conclusions: Mutation rates differed among patients according to their disease history. Difference of mutation between primary tumor and metastatic lesion were larger than technical noise and the heterogeneity of primary cancers was larger than that of metastasis. Metastasis often differed from the primary tumor in the spectrum of potentially targetable anomalies.
Plasma adiponectin to predict incident cancer in a large multiethnic population-based cohort study.
Authors: Beg Muhammad Shaalan , Saleem Sadia , Turer Aslan , Ayers Colby , Zhang Song , Scherer Philipp , Lakoski Susan 
Published: March 2020

1560 Background: Previous retrospective studies have suggested an inverse relationship between cancer and markers of insulin resistance, including adiponectin. Whether circulating levels of adiponectin are associated with future cancer incidence has not been well demonstrated. As such, we examined the association of adiponectin on the risk of future cancer development in a large population based cohort study. Methods: The Dallas Heart Study (DHS) is a multiethnic population based study of 3,531 Dallas County residents with an intentional oversampling of minorities which are underrepresented in other population studies. Incident and prevalent cancer cases were identified in the DHS by the Texas Cancer Registry. Cases were defined as ‘incident’ if they were diagnosed 24 months after enrollment into DHS. Fasting blood samples were obtained from DHS participants between 2000 and 2002, and used for biomarker analysis. Univariate and multivariate analysis was performed to test the association of incident cancer and adiponectin after adjusting for age, diabetes status, gender, ethnicity and body mass index (BMI). Results: Of 3,531 individuals, 150 incident cancer cases were diagnosed. The study population comprised 55.8% females, 51.5% were black and 39.6% had a BMI above 30 kg/m2. Mean adiponectin was 8.12 μg/ml in incident cancer group and 7.46 μg/ml in non-cancer group (p=0.129). In multivariable analysis, adiponectin was not an independent predictor of cancer incidence after adjusting for age, diabetes status, gender, ethnicity and BMI (p=0.167) Conclusions: Previous population based studies have demonstrated conflicting results on the association of markers insulin resistance, including adiponectin, and cancer incidence. In this study of a predominant ethnic minority population, an association between adiponectin and cancer incidence was not seen. Further prospective studies are needed to understand the association between markers of insulin resistance and risk of future cancer risk.
Public awareness of the HPV vaccine: A national population-based study.
Authors: Shrader Abigail , Niccolai Linda , Mayne Susan T , DiMaio Daniel , Chagpar Anees B. 
Published: March 2020

1574 Background: Human papilloma virus (HPV) is associated with a number of malignancies. While national guidelines exist for the use of HPV vaccines in men and women up to the age of 26, data are lacking regarding public awareness of these vaccines. Methods: The National Health Interview Survey is conducted annually by the CDC, and is designed to be representative of the US population. Questions regarding the HPV vaccine were fielded in 2010, and formed the basis of this analysis. Results: 9120 men and 10946 women between the ages of 18 and 64 were surveyed. More women than men had heard about the HPV vaccine (68.1% vs. 34.0%, p<0.001), and young people (aged 18-26) were more likely to have heard about the vaccine than their older counterparts (54.3% vs. 50.5%, p=0.002). Factors associated with awareness of HPV vaccines amongst the younger cohort (eligible for the vaccine) are shown below. On multivariate analysis, race, insurance, and education were significant predictors of HPV vaccine awareness. Conclusions: While over half of young people aged 18-26 are aware of the HPV vaccine, racial/ethnic minorities, along with less educated and uninsured populations lag behind their majority counterparts in their awareness of the HPV vaccine. These data should be useful in directing public health educational programs. [Table: see text]
Individual insulin use and the risk of breast cancer: An international clinical epidemiology study.
Authors: Grimaldi-Bensouda Lamiae , Cameron David A. , Marty Michel , Barnett Anthony H , Penault-Llorca Frederique , Pollak Michael N. , Charbonnel Bernard , Riddle Matthew , Mignot Laurent , Boivin Jean-Francois , Khachatryan Artak , Rossignol Michel , Benichou Jacques , Alperovitch Annick , Abenhaim Lucien ,   ISICA Group
Published: March 2020

1578 Background: The association between individual insulin use and cancer risk has been previously considered with studies reporting higher breast cancer incidence for insulin glargine. Objective: To assess the relative risk of breast cancer associated with individual insulin use (glargine, human insulin, insulin analogs aspart and lispro). Methods: Systematic case-control study of incident breast cancer occurring in women with diabetes from across the United Kingdom, Canada and France. Participants and Settings: 775 case-patients with diabetes and primary invasive or in situ carcinoma of the breast (diagnosed between 1 January, 2008 and 30 June, 2009) selected from 39,958 incident breast cancer patients from 92 large oncology clinics; and 3,050 control-patients with diabetes selected from 580 general practices and matched on country, age, date, type of diabetes (1 or 2), and management by diabetologist or general practitioner. Data on exposure: Data was collected from physicians and patients. Statistical analysis: The main risk model was a multivariable conditional logistic regression including individual insulin use, 8 years preceding the index date, and controlling for past use of any insulin, oral antidiabetic drug use, reproductive factors, lifestyle, education, hormone replacement therapies and contraceptive use, body mass index, comorbidities, diabetes duration, and annual number of physician visits. Results: Adjusted odds ratios of breast cancer were: 1.04 [95% Confidence Interval: 0.76-1.44] for glargine; 1.23 [0.79-1.92] for lispro; 0.95 [0.64-1.40] for aspart; 0.81 [0.55-1.20] for human insulin. Similar results were observed in new insulin users. No effect of dose or duration of use was observed for glargine on the risk of breast cancer. Conclusions: This first international case-controlled study found no difference in the risk of developing breast cancer among patients according to individual insulin use.
Abnormal bone marrow signal on MRI heralding oncologic diagnoses: A single institution review.
Authors: Shah Gunjan L. , Jarboe Jamie Michelle Bunch , Rosenberg Aaron Seth , Klein Andreas Kirschmer , Cossor Furha Iram 
Published: March 2020

1580 Background: The increased use of magnetic resonance imaging (MRI) has resulted in increased numbers of incidental findings. Oncologists often receive consults for workup of "abnormal marrow signal." As there is no standard evaluation for such findings and the yield of additional evaluation is unclear, we performed a retrospective study of patients evaluated with MRI at Tufts Medical Center (TMC). Methods: With IRB approval, TMC radiology reports were searched from 5/9/05-12/31/08 with GE Centricity Radiology Information System 2.2. Included patients had MRI reports containing the phrases “abnormal bone marrow” or “heterogeneous bone marrow”, but no clear etiology stated. Further workup, including referral to a subspecialist, laboratory, radiographic, or pathologic evaluations, final diagnosis, and last follow up were collected. Results: 29,508 MRIs were performed and 77 patients met search criteria. Median age was 58 years with a median follow-up of 41 months at TMC after qualifying MRI. 40/77 (52%) of patients had either an MRI of the lumbar spine or hip with 21/77 (27%) undergoing work-up for the marrow findings. Evaluations included CBC (38%), SPEP (24%), quantitative immunoglobulins (14%), free light chains (10%), peripheral blood flow cytometry (5%), bone marrow biopsy (19%), skeletal survey (14%), bone scan (48%), CT scan (24%), biopsy of other site (24%), and subspecialty referal (48%, 29% to oncology). Definitive diagnosis was assigned in 11/21 (52%) cases, with 5 being malignancies (1 follicular lymphoma, 2 multiple myeloma, 2 lung cancer). Three patients were later diagnosed with malignancy (breast cancer, myelodysplastic syndrome, merkel cell carcinoma) at a median of 19 months. Overall, 10% of patients with abnormal marrow on MRI were diagnosed with a malignancy. Conclusions: Incidentally noted abnormal or heterogeneous bone marrow signal on MRI was not inconsequential. Of those patients who underwent evaluation for the finding, 24% were diagnosed with a malignancy. We conclude that abnormal bone marrow findings on MRI should not be ignored, and given the rates of malignancy in our series, oncologists are ideally suited for this task.
Association of PIK3CA mutations and age with the occurence of second primary lung cancer (SPLC).
Authors: Bos Marc Christiaan Allardt , Gardizi Masyar , Scheffler Matthias , Nogova Lucia , Zander Thomas , Heukamp Lukas Carl , Schildhaus Hans-Ulrich , Merkelbach-Bruse Sabine , Fassunke Jana , Binot Elke , Schlesinger Andreas , Geist Thomas , Kambartel Kato , Schnell Roland , Schulz Holger , Behringer Dirk M. , Serke Monika , Schmitz Stephan H. , Randerath Winfried , Wolf Juergen 
Published: March 2020

1589 Background: The incidence of SPLC in Germany was reported to be 1.2 per 100,000 inhabitants in 2007 and the prevalence of second primary cancers reported by the US International Cancer Institute's Surveillance, Epidemiology and End Results Program has more than doubled over the last 25 years. Recently there has been tremendous progress in the ability to detect driver mutations in lung cancer and large studies presented the frequencies of driver mutations in unselected patient populations. We conducted an association study of known genetic driver events and clinical characteristics with the occurence of SPLC. Methods: Within the Network Genomic Medicine Lung Cancer, a local molecular screening network encompassing hospitals and office-based oncologists in the catchment area of the Center for Integrated Oncology Köln Bonn, we retrospectively reviewed the medical records of 375 molecularly annotated NSCLC patients for their SPLC status and clinical characteristics (age at diagnosis, histology, sex, smoking status). Molecular analysis for lung adenocarcinoma included the EGFR, ALK, BRAF, KRAS and PIK3CA status and for squamous cell lung cancer the FGFR1 and PIK3CA status. Results: 84 of 375 (22,4%) patients were SPLCs. The median age of SPLC diagnosis was 70 yrs. (Range 53 - 85 yrs.) and differed significantly from the rest of the population with a median age of 65 yrs. (Range 28 - 86 yrs.). The frequency of SPLCs was not significantly different between males and females (p = 0,259). In univariate logistic regression analysis active and former smoking, positive PIK3CA mutation and FGFR1 amplification status as well as age were significantly associated with the occurrence of SPLC. In a multivariate logistic regression analysis including the variables mentioned above only PIK3CA mutations (OR 9,48 95% CI 1,83 - 49,1) (p = 0,007) and age (OR 1,06 95% CI 1,03 - 1,1) (p = 0,015) could be confirmed to be independent prognosticators for the occurrence of SPLCs. Conclusions: The occurrence of SPLC was associated with age and PIK3CA mutations in our study population. Further comprehensive investigations on this topic are needed to confirm our findings and to further understand the association between mutation status and SPLCs.
Neurologic, vascular, and endocrine morbidity following childhood exposure to low and moderate doses of ionizing radiation.
Authors: Sadetzki Siegal , Chetrit Angela , Boursi Ben , Sikron Fabienne 
Published: March 2020

1599 Background: While the association between exposure to ionizing radiation and cancer is well known, its possible role in the development of other diseases e.g. in the vascular, neurologic and endocrine systems is limited and inconsistent. The aim of this study was to assess the effect of childhood exposure to low and moderate doses of radiation on the development of chronic diseases (other than cancer) based on a large cohort followed for 55 years. Methods: The study population included an exposed group of 13,158 individuals treated with ionizing radiation for tinea capitis and a comparison group of 16,225 unexposed subjects. The mean dose to the head and the thyroid gland were 1.5 Gy and 0.094 Gy respectively and the mean age at exposure was 7.1±3.1y. Data on the outcome variables was obtained through computer linkage of the study database with the largest health care provider registry in Israel. Results: Of the study population, 64% were found to be insured in this heath provider (66.8% among the irradiated and 63.6% among the unexposed group). The two study groups did not differ in current age (mean 62.1+4.5 y), gender, marital status, smoking and BMI. Compared to the unexposed group, the irradiated group demonstrated a significantly (p<0.001 ) increased prevalence of epilepsy (1.8% vs. 2.8%), CVA (6.4% vs. 8%), diabetes (26.5 % vs. 28.2%), hyperthyroidism (8.1% vs. 9.4%), hyper/hypo-parathyroidism (0.6% vs. 1.2%) and depression (8.1% vs. 9.4%), respectively. There was no statistical difference between the groups in the prevalence of dementia and Parkinson's disease. Multivariate models accounting for different variables of interest (e.g. age at exposure, gender, SES) will be presented. Conclusions: These results have practical implications for primary prevention and early detection of therapeutic and diagnostic radiation associated morbidity.
Prevalence and patterns of cancer in patients with congenital disease: A national-based cohort study.
Authors: Lin Po-Han , Muo Chih-Hsin , Li Long-Yuan , Yang Hwai-I , Chiu Chang-Fang , Tsai Fuu-Jen 
Published: March 2020

1600 Background: Association of congenital disease (CD) and malignancy was noted in some studies. However, the cancer risk and patterns of different CD was unclear. In this study, we aimed to assess and quantify the relationships between CD and cancers. Methods: In the National Health System of Taiwan, 2.9 million children were born between 1998 and 2010. Patients with CD were identified using ICD-9-CM 740-759. Cox’s proportional hazards regression analysis was used to assess the cancer risk of CD. Results: A total of 32358 CD patients were identified and 87 of them developed malignancy. The cancer diagnostic age was significantly younger in patients with CD (2.44 ± 2.28 years) than patients without CD (3.97 ± 3.04 years; p<0.001). The hazard ratio (HR) of cancer incidence was 2.70 (95% confidential interval (CI) 2.12-3.44). Subgroup analysis showed that significantly increased risk of cancer development was noted among patients with cardiac anomalies (N=26, HR=1.91, 95% CI 1.28-2.86), digestive anomalies (N=8, HR=3.32, 95% CI 1.64-6.70), cutaneous anomalies (N=2, HR=21.5, 95% CI 5.35-86.40) and chromosomal anomalies (N=29, HR=17.5, 95% CI 12.00-25.70); other congenital diseases did not. Considering cancer types, patients with cardiac anomalies had higher rate of hematological cancers (N=12, HR=2.09, 95% CI. 1.15-3.79), especially acute myeloid leukemia (AML; N=9, HR=12.2, 95% CI. 5.36-28.0). Patients with digestive anomalies also had higher rate of hematological cancers (N=4, HR=3.95, 95% CI. 1.46-10.70), and the dominant type was non-Hodgkin lymphoma (N=2, HR=14.70, 95% CI. 3.38-64.0). Patients with chromosomal anomalies had superior rate to have retroperitoneal sarcoma (N=1, HR=8.54, 95% CI. 1.14-63.90), anterior mediastinal tumor (N=1, HR=8.54, 95% CI. 1.14-63.90), and hematological cancers (N=23, HR=33.20, 95% CI. 21.20-51.80), especially the AML (N=21, HR=231, 95% CI. 119-448). Down syndrome patients had extremely high risk of AML (N=8, HR=388, 95% CI. 164-918). Conclusions: Patients with cardiac, digestive, cutaneous and chromosomal CD were at increased risk and younger age to develop cancer. Hematological malignancies, especially AML, were the most common cancer type among these patients.
A randomized phase II study of bevacizumab versus bevacizumab plus lomustine versus lomustine single agent in recurrent glioblastoma: The Dutch BELOB study.
Authors: Taal Walter , Oosterkamp Hendrika M , Walenkamp Annemiek M.E. , Beerepoot Laurens Victor , Hanse Monique , Buter J. , Honkoop Aafke , Boerman Dolf , De Vos Filip Yves Francine Leon , Jansen Rob L. , van den Berkmortel Franchette W.P.J. , Brandsma Dieta , Kros Johan M , Bromberg Jacoline E , van Heuvel Irene , Smits Marion , van der Holt Bronno , Vernhout Rene , Van Den Bent Martin J. ,   Landelijke Werkgroep voor NeuroOncologie
Published: March 2020

2001 Background: Bevacizumab (BEV) is widely used in recurrent glioblastoma, alone or in combination with other agents. There is however no well-controlled trial to support the use for this indication. Methods: In a three-arm Dutch multicenter randomized phase II study (NTR 1929) patients were assigned to either BEV 10 mg/kg iv every 2 weeks, BEV 10 mg/kg iv every 2 weeks and 110 mg/m2 lomustine every 6 weeks, or lomustine 110 mg/m2every 6 weeks. Eligible were patients with histologically proven glioblastoma, with a first recurrence after chemo-irradiation with temozolomide, having concluded radiotherapy more than 3 months ago, with adequate bone marrow, renal and hepatic function, and WHO performance status (PS) 0-2. Primary endpoint was 9 months overall survival (OS); P0 was set at 35% and P1 at 55%. Progression was defined using RANO criteria. A safety review after the first 10 patients in the combination arm was preplanned. Results: Between December 2009 and November 2011, 153 patients were enrolled of whom 148 were considered eligible. Median age was 57 years (range, 24-77) and median WHO PS was 1. With respect to prognostic factors groups were well balanced. After review of the safety cohort the dosage lomustine in the combination arm was lowered to 90 mg/m2 because of hematological toxicity (predominantly thrombocytopenia without symptoms). At this lower lomustine dose level the combination treatment was in general well tolerated. Outcome: see Table. Conclusions: In this first well-controlled study on BEV in recurrent glioblastoma with a primary OS endpoint, combination treatment with bevacizumab and lomustine met the prespecified criterion for further investigation in clinical trials, whereas both drugs given as single agent failed to meet this criterion. Clinical trial information: NTR1929. [Table: see text]
Tumor response based on adapted Macdonald criteria and assessment of pseudoprogression (PsPD) in the phase III AVAglio trial of bevacizumab (Bv) plus temozolomide (T) plus radiotherapy (RT) in newly diagnosed glioblastoma (GBM).
Authors: Wick Wolfgang , Cloughesy Timothy Francis , Nishikawa Ryo , Mason Warren , Saran Frank , Henriksson Roger , Hilton Magalie , Kerloeguen Yannick , Chinot Oliver L. 
Published: March 2020

2002^ Background: Until recently the primary criteria for assessing response to GBM therapy were those by Macdonald et al. (JCO 1990;8:1277–80). Advances in imaging technology/targeted therapies exposed limitations, addressed in 2010 by Response Assessment in Neuro-Oncology Working Group. Prior to this, the AVAglio study similarly adapted Macdonald criteria to address anti-angiogenic therapy/corticosteroid use by incorporating non-contrast-enhancing components and integrating a strict algorithm to standardize assessment of possible PsPD. Methods: Randomisedpts (n=921) received: T/RT + Bv or placebo (P), 6 wks; 28-d break; maintenance T + Bv or P (6 cycles); monotherapy Bv or P until PD/unacceptable toxicity. Tumor response was investigator (inv)-assessed by MRI (adapted Macdonald criteria) at baseline (BL), end of break, every 2nd maintenance cycle, every 9 wks during monotherapy, at PD and 9 wks post-PD. PsPD was inv-assessed at the end of the break. A ≥25% increase in index lesions and/or unequivocal progression of existing non-index lesions relative to BL and in the absence of clinical deterioration was assessed as PsPD. Confirmatory PsPD assessment: end of the 2nd maintenance cycle. If progression was confirmed, PsPD was retrospectively designated as PD. If PsPD was confirmed, pts remained on treatment and the 1st post-RT MRI was used as a new BL. Best ORR was evaluated in pts with lesions at BL, excluding pts with confirmed PsPD. Results: Co-primary endpoint of inv-assessed PFS was longer for pts receiving Bv+RT/T compared with P+RT/T (HR 0.64, 95% CI 0.55–0.74; p<0.0001). Best ORR and PsPD are shown (Table). Conclusions: Addition of Bv to 1st-line T/RT significantly improves ORR. The rate of confirmed PsPD was low in both arms. Clinical trial information: NCT00943826. [Table: see text]