bluuebunny/crossref_metadata_2025_split huggingface dataset:
What puts physicians and patients discussing cancer screening on the same page?
Authors: Seiden Danielle , Bezuhly Maureen , Aharanoff Gina , Cassano Kelly , Osborne Michael P. , Chadha Manjeet , Talcott James Austin 
Published: September 2018

1552 Background: Shared decision making requires effective provider-patient communication. We studied concordance in recalled discussions and factors that affected it. Methods: In a cluster-randomized trial of educational supports for providers (MDs), we are enrolling an age-(30-89 years) and sex-stratified sample of 216 patients (PTs) who underwent a physical examination at 2 urban hospitals, 18 for each of 12 primary care MDs. Screening guideline formatting (colorcoding) and academic detailing were randomly assigned in a 2x2 design. Immediate post encounter surveys recorded PT and MD recall of screening discussions. Results: The first 174 participants were diverse (63% white) and highly educated (77% college degree). PTs and MDs differed in recall of screening discussions, and the differences varied by screening test. When MDs reported a colorectal cancer (CRC) screening discussion, 21% of PTs did not; 20% of MDs disagreed when PTs reported the discussion. The discrepancies were greater for prostate specific antigen (PSA) screening, 29% and 29%, respectively, but much less for mammograms (MAM), 8% and 5%, respectively. Recall of the MD recommendation also differed: 15% of PTs disagreed when their MD reported it, and 33% of MDs when their PT reported it. For PSA, disagreement was 26% and 33%, respectively, and for MAM, disagreement was 17% and 10%, respectively. Overall, agreement between all PTs and MDs on whether screening was recommended was fair for CRC, PSA and MAM: kappa = 0.33, 0.34 and 0.29, respectively. For PTs > 70 agreement was nonexistent on recalled CRC and PSA recommendations (kappa = -0.02 and -0.03, respectively) but preserved for MAM (kappa = 0.39). Sex did not affect CRC agreement. Recall concordance improved when SDM was recalled. For CRC, kappa rose from -0.12 to 0.52 if the MD recalled any MDM element. Conclusions: In a highly educated, diverse patient population, patients and physicians often disagreed on recalled cancer screening discussions. Discordance was greatest with PSA and least with MAM. Discordance was greater in older patients. If MDs recalled any shared decision making, agreement increased significantly. Communication varies by cancer screen, PT age and elements of shared decision making. Clinical trial information: NCT02430948.
Incidence and survival trends of cancers diagnosed in young adults (20-39 years): A population-based study.
Authors: Olga Husson , van der Mark Marianne , Bijlsma Rhode , Westermann Anneke M. , Aben Katja , Van Der Graaf Winette T.A. 
Published: September 2018

1567 Background: Cancer in young adults (YAs; 20–39 years) is rare but its incidence is increasing globally. In The Netherlands, care for YA cancer patients is mostly dispersed, in contrast to centralized care for all pediatric cancer patients. Aim of this population-based study was to examine trends in YA cancer incidence and survival. Methods: Data from all YAs diagnosed between 1989-2015 (n = 89,675) were obtained from The Netherlands Cancer Registry. Age-standardized incidence rates with estimated annual percentage of change and five-year relative survival rates were calculated. Results: Cancer incidence in YAs increased significantly from 48 to 67 per 100,000 person years in males (1.7%) and from 78 to 97 per 100,000 person years in females (1.1%). In both males and females, significant rising incidence trends were found for melanoma (2.3%), skin (2.3%) and thyroid cancer (3.2%), CML (7.2%), Hodgkin (1.3%) and Non-Hodgkin lymphoma (0.9%). In females, the incidence of breast cancer increased (1.2%), while it decreased for lung (-1.3%) and ovarian cancer (-4.3%). In males, testicular cancer incidence increased significantly (4.1%). The most common cancers in male YAs were testicular cancer (33%), melanoma (15%), gastrointestinal cancer (8%), Non-Hodgkin and Hodgkin lymphoma (both 7%), whereas in females breast cancer (34%), melanoma (19%), gynecological (14%), thyroid and gastro-intestinal cancer (both 5%) were most frequently diagnosed. Over time, the five-year relative survival increased significantly from 72% to 85%. Survival improved for almost all tumor types, except for pediatric tumors: medulloblastoma (~60%), Ewing sarcoma (~43%) and rhabdomyosarcoma (~41%). A < 80% five-year survival rate was also found for tumors of the lung (36%), gastro-intestinal tract (61%), ALL (60%), AML (65%) and soft tissue sarcomas (77%). Conclusions: Over the last 26 years, a marked increase in the incidence of a diverse spectrum of hematological and solid malignancies, pediatric and adult-type cancers was found for YAs. Survival improved over time, however remains poor for certain tumor types. Our data underpin the importance of knowledge of tumors at YA age to guide centralization of care and clinical research.
Association of dietary fiber intake and gut microbiota in healthy adults.
Authors: Lin Daniel , Peters Brandilyn , Sinha Rashmi , Goedert James J. , Hayes Richard , Ahn Jiyoung 
Published: September 2018

1569 Background: Increasing evidence has shown that gut microbiota alterations may play a role in colorectal cancer risk. Diet, particularly fiber intake, may modify gut microbiota composition, which may consequently impact cancer risk development. We investigated the relationship between dietary fiber intake and gut microbiota in healthy humans. Methods: Using 16S rRNA gene sequencing, we assessed gut microbiota in fecal samples from 151 healthy adults in two independent study populations: Study A, n = 75 (healthy controls from a colorectal cancer case-control study), and Study B, n = 76 (polyp-free subjects from a cross-sectional colonoscopy study). We calculated energy-adjusted total dietary fiber intake of participants based on food frequency questionnaires. For each study population, we evaluated the relationship between quartiles of higher fiber intake as a continuous ordinal variable, and global gut microbiota community composition (via PERMANOVA of weighted UniFrac distance) and specific taxon abundance (via DESeq2). Results: We found that fiber intake was significantly associated with overall microbial community composition in Study B (p = 0.003) but not Study A (p = 0.68), after adjustment for age, sex, race, body mass index, and cigarette smoking. In a taxonomy-based meta-analysis of these two study populations, higher fiber intake was associated with lower abundance of genus Actinomyces (fold change [FC] = 0.769, p = 0.003), and higher abundance of genera Faecalibacterium (FC = 1.153, p = 0.03), Lachnospira (FC = 1.167, p = 0.04), and SMB53 (FC = 1.201, p = 0.05). A species-level meta-analysis showed an association between higher fiber intake and higher abundance of Faecalibacterium prausnitzii (FC = 1.165, p = 0.03) and lower abundance of Ruminococcus bromii (FC = 0.828, p = 0.08). Conclusions: Our results suggest that higher intake of dietary fiber may alter gut microbiota in healthy adults. Given the potentially modifiable nature of the gut microbiota through diet, these findings warrant further study of diet-microbiota based colorectal cancer prevention strategies.
Does race play a role in genetic screening for hereditary cancer syndromes?
Authors: Chatterjee Sudeshna , Frey Melissa K , Zhou Zhen Ni , Carlson Ann , Caputo Thomas A. , Holcomb Kevin , Chapman-Davis Eloise 
Published: September 2018

1578 Background: Molecular analysis of cancer predisposition genes may influence cancer screening, prevention strategies and options for targeted therapy. We sought to identify ethnic differences in patterns of genetic testing. Methods: Results of all patients with known ancestry who underwent genetic testing at the hereditary breast and ovarian cancer center at a single institution between 7/1/2013-12/31/2016 were reviewed. Race was stratified as Black, White, Asian, and Hispanic. Ashkenazi Jews were excluded from the White subgroup because of their higher rates of testing for deleterious founder mutations. White patients were utilized as the reference population for all statistical analysis. Results: 894 patients were included: 139 Black, 613 White, 33 Hispanic and 108 Asian. Black patients were more likely to undergo genetic testing for a personal history of cancer rather than family history risk assessment compared to White patients (p = 0.002). There was no difference in genetic testing rates based on personal or family history of cancer between Asians or Hispanics and Whites (p = 0.398 ;p = 0.366). Black patients were more likely than White patients to undergo testing with targeted-gene rather than multigene panels (p = 0.026). The use of targeted and multigene panels were not different among Asians or Hispanics ( p = 1.0). Blacks, Asians and Hispanics had a lower rate of known deleterious mutations but a higher rate of variants of unknown significance (VUS) than Whites (15.1% p = 0.048; 22.2% p = .001; 33.3%p = .002 respectively). BRCA1/2 mutations accounted for 100% of identified mutations across all the non-White populations. Among Blacks, BRCA1/2 accounted for 38.1% of VUS compared to 27.9% in Whites ( p = .2114). VUS in the ATM gene accounted for 28.6% in Blacks compared to 8.2% in Whites (p = 0.028). Conclusions: Black patients were less likely to undergo testing based on family history, suggesting a missed opportunity for cancer prevention. They were more likely to undergo targeted testing and100% of identified mutations were in BRCA1/2 genes. Non-white patients had higher rates of VUS, emphasizing the need for improved VUS reclassification in non-White populations.
Patterns of genetic screening for hereditary cancer syndromes: Effect of Supreme Court’s ruling invalidating single gene patent rights.
Authors: Zhou Zhen Ni , Frey Melissa K , Nasioudis Dimitrios , Carlson Ann , Fields Jessica , Holcomb Kevin , Chapman-Davis Eloise 
Published: September 2018

1580 Background: In 6/2013 the Supreme Court ruled that isolated DNA sequences found in nature could not be patented, resulting in rapid uptake of multigene panels. We sought to explore trends in genetic testing since this ruling. Methods: Results of all patients undergoing genetic testing and counseling at a single institution between 7/1/13 and 12/31/16 were reviewed. Associations between categorical variables were evaluated by chi-square tests or Fisher's exact tests as appropriate for category size. Results: 1663 patients underwent genetic testing over the study period. The median age was 49 years (range 18-86). Use of multigene panels versus targeted gene testing increased significantly in the years following the Supreme Court ruling (Table 1, P<0.001). While the percentage of patients found to have pathogenic mutations remained stable over the study period (9%), detection of variants of uncertain significance (VUS) increased significantly (Table 1, P<0.001). In 2013 BRCA1/2 mutations accounted for 91% of identified mutations; however this number decreased over time (2014-83%, 2015-70%, 2016-58%, P=0.01). Use of multigene panels detected 71% of mutations in non- BRCA1/2 genes such as CHEK(19), APC(44), MSH6(1), P53(1), and PTEN(1). Patients with a personal history of breast and/or ovarian cancer were more likely to have targeted testing than patients with other cancer types (590, 66% vs. 9, 33%, P=0.001). Conclusions: The uptake of multigene panels has increased since the 2013 Supreme Court ruling. While this technology allowed for the identification of many cancer-related genes that would be missed on targeted BRCA1/2 testing, it also resulted in a significantly increased detection of VUS, a finding with unknown clinical implications. [Table: see text]
VHVT: An ultra-sensitive somatic mutation detection and performance assessment program.
Authors: Liu Jilong , Liu Zu , Cheng Shaomin , Guo Fengming , Tan Meihua , Wang Jingjing , Shao Di , Zhang Pan , Li Zhilong , Liu Han , Li Shiyong , Hu Zhenfei , Hou Yumei , Mao Mao , Ye Mingzhi 
Published: September 2018

1588 Background: NGS as a high throughput technique is particular valuable for cancer given its ability to detect multiple driver mutations. While reads contain SNVs and short InDels can be mapped to the right position using gatk-like programs, a program designed for germline mutation detection, reads contain long InDels such as EGFR EX19 deletions often wrongly mapped especially when deletions near the ends of the reads. Thus, gatk would not recognize these reads, consequently underestimate the mutation allelic frequency, and even missed out InDels when supporting reads were rare. Methods: Here we present a variation hotspot validation toolkit (VHVT), a validation based method to precisely detect the ultra-low frequency somatic mutations. As far as we know, it is the first specialized somatic mutation detection software. First, reference sequences aimed at the hotspot mutations were assembled, then reads were be mapped to the new assembled reference to precisely distinguish the supporting reads. Moreover, log odds (LOD) and Poisson mathematical model were integrated to control sequencing error, as a result, VHVT can achieve a limitation of detection at 0.01% with sensitivity and specificity above 95% and 99% respectively. In addition, we developed a method to quantitatively assess the performance of variation detection program using standard reference data. By mapping to the reconstructed reference, all supporting reads will be detected in sequencing data, and comparing theses with the number of supporting reads delivered by a program we can define recognition ratio of supporting reads. Results: Our reference standard data showed that VHVT can recognize average 30% more support reads than gatk for EGFR EX19 deletions. In a total 498 NSCLC clinical samples test, VHVT detected actionable mutations in 289 samples. 243 positive mutations were verified (168 by SANGER sequencing, 75 by ddPCR) with concordance rate at 100%. Conclusions: Taken all together, our results demonstrated the robust performance of VHVT for somatic mutation detection and program assessment and thus facilitate the development of personalized cancer therapy.
Randomized, double-blind, phase III trial of a personalized peptide vaccination for human leukocyte antigen-A24-positive glioblastoma multiforme patients refractory to temozolomide-based therapy.
Authors: Terasaki Mizuhiko , Narita Yoshitaka , Arakawa Yoshiki , Sugiyama Kazuhiko , Aoki Tomokazu , Kanamori Masayuki , Nagane Motoo , Kumabe Toshihiro , Hirose Yuichi , Ichikawa Tomotsugu , Fujimaki Takamitsu , Kobayashi Hiroyuki , Goto Hisaharu , Takeshima Hideo , Ueba Tetsuya , Abe Hiroshi , Tamiya Takashi , Sonoda Yukihiko , Kakuma Tatsuyuki , Nishikawa Ryo 
Published: September 2018

2000 Background: To establish whether personalized peptide vaccination (PPV) is clinically beneficial for human leukocyte antigen (HLA)-A24-positive glioblastoma multiforme (GBM) patients refractory to temozolomide (TMZ)-based therapy. Methods: From January 2012 to March 2016, 88 HLA-A24-positive GBM patients refractory to TMZ-based therapy from 20 Japanese hospitals were randomly assigned to receive PPV treatment (n = 58) or best supportive care (BSC) (n= 30) at a 2 to 1 ratio. Four peptides chosen from 12 peptide candidates based on pre-vaccination IgG levels specific to each peptide or 4 corresponding placebos were injected subcutaneously once weekly for 12 times at the first course followed by biweekly vaccinations until disease progression. The primary endpoint was overall survival (OS). Results: The primary endpoint was not met in this clinical trial. Unfavorable prognostic factors were performance status (PS) 3, higher plasma levels of pre-vaccination granulocyte macrophage-colony stimulating factor (GM-CFS), and PPV containing SART2-derived peptides. Therefore, 78 patients with PS of 0 to 2 (50 with PPV and 28 with BSC) were provided for the subgroup analysis. Among them, the median OS of 39 PPV patients (10.4 months, 95% CI, 7.8-12.0 months) who had either lower levels of GM-CSF ( < 0.9 pg/mL) or 4 peptide vaccinations that did not include SART2-derived peptides was significantly (p = 0.03) longer than that of the corresponding 19 BSC patients (6.8, 4.6-12.7). In contrast, the median OS of 10 PPV patients (4.1, 1.1-8.3) who had both higher levels of GM-CSF ( > 0.9 pg/mL) and 4 peptide vaccinations containing SART2-derived peptides was significantly (p = 0.01) shorter than that of the corresponding 9 BSC patients (not reached, 1.6-not reached). A single grade 3 adverse event was the only PPV-related adverse event of grade > 3 in this study. Conclusions: PPV monotherapy could be a new treatment modality for HLA-A24-positive GBM patients refractory to TMZ-based therapy, since this approach showed clinical benefit and safety under precision medicine-based pre-vaccination selection of appropriate patients. Clinical trial information: UMIN000006970.
Final results of the EORTC Brain Tumor Group randomized phase II TAVAREC trial on temozolomide with or without bevacizumab in 1st recurrence grade II/III glioma without 1p/19q co-deletion.
Authors: Van Den Bent Martin J. , Klein Martin , Smits Marion , Reijneveld Jaap C. , Idbaih Ahmed , Clement Paul , De Vos Filip Yves Francine Leon , Wick Wolfgang , Mulholland Paul James , Taphoorn Martin J.B. , Lewis Joanne , de Heer Iris , Kros Johan M , Verschuere Tina , Golfinopoulos Vassilis , Gorlia Thierry , French Pim ,   EORTC Brain Tumor Group
Published: September 2018

2009 Background: Although bevacizumab (BEV) is frequently used in recurrent grade II and III glioma without 1p/19q co-deletion, this use is without evidence from randomized trials. Methods: The TAVAREC trial (NCT01164189) is a randomized phase II study in locally diagnosed non-1p/19q co-deleted grade II or III glioma, with a first and contrast-enhancing recurrence after initial radiotherapy. Prior chemotherapy was allowed provided patients were at least 6 months off treatment. Patients were treated with either 200mg/m2 temozolomide (TMZ) day 1-5 every 4 weeks for a maximum of twelve cycles, or with the same TMZ regimen in combination with BEV 10 mg/kg every 2 weeks until progression. Response, Quality of Life (QOL, using the EORTC QOL C30/BCM20 questionnaire) and neurocognitive function (NCF) using a standardized test battery with Hopkins Verbal Learning, Trail Making test A/B and Controlled Oral Word Association were evaluated every 3 months. Primary endpoint is the Overall Survival (OS) rate at 12 months (OS12). Tumor samples were centrally analyzed for MGMT status (Illumina methylation arrays) and IDH1/2 mutations ( IDHmt). Results: Between 8/2/2011 and 31/7/2015, 155 patients were randomized; median age was 44 years, 88 (70%) of 125 tested tumors showed an IDHmt, 27% of patients had received prior chemotherapy. OS12 was 61% in the TMZ arm and 55% in the TMZ+BEV arm, with overlapping OS and progression free survival (PFS) Kaplan Meier curves and similar response rates (TMZ: 42%; TMZ + BEV: 49%). Post-progression, 33% of the TMZ and 17% of the TMZ + BEV patients received BEV. OS was longer in IDHmt tumors compared to IDH wild type tumors (15 mo vs 10.7 mo, p = 0.001) but PFS was clinically similar (6.7 mo vs 5.1 mo, p = 0.056). IDH mutational status was not predictive for benefit to BEV. Compliance to NCF testing and QOL was above 60% in the 1st year. At the group level, NCF was similar in the TMZ and in the TMZ+BEV patients. QOL and MGMTresults will be presented at the meeting. Conclusions: The addition of BEV to TMZ does not improve OS, PFS, or cognitive function in recurrent grade II and III 1p/19q intact gliomas; regardless of IDH mutational status. Clinical trial information: NCT01164189.
Identification of novel therapeutic targets in glioblastoma with functional genomic mRNA profiling.
Authors: Brahm Cyrillo Gerardo , Walenkamp Anna Maria Elisabeth , Van Linde Myra Ellen , Verheul Henk M.W. , Fehrmann Rudolf Stephan Nicolaas 
Published: September 2018

2018 Background: Glioblastoma (GBM), the most common primary brain tumor in adults, universally recurs and has a dismal prognosis. Therefore, there is an unmet need for new and more effective treatment strategies. Here, we aim to discover new therapeutic targets by identifying upregulated genes in GBM with known antineoplastic drug interactions. Methods: Publicly available, raw microarray expression data of patient-derived GBM samples and normal brain tissue were collected from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Subsequently, we applied functional genomic mRNA profiling (FGmRNA-profiling), a method that is able to correct the gene expression profile of an individual tumor for physiological and experimental factors, which are considered not to be relevant for the observed tumor phenotype. Next, the FGmRNA-profiles of healthy brain tissue and glioblastoma were used to perform a class comparison analysis. Significantly upregulated genes in GBM were prioritized based on: known interaction with antineoplastic agents and the current status of clinical evaluation in humans. Results: After FGmRNA-profiling 66 normal brain tissue samples and 1280 patient-derived GBM samples, class comparison identified 712 significantly upregulated genes. Of all significantly upregulated genes, 27 genes interacted with antineoplastic drugs. 17 out of these 27 druggable genes, including EGFR and VEGFA, have already been clinically evaluated in GBM, and had limited efficacy. Out of the 10 remaining druggable genes, we prioritized RRM2, MAPK9 and XIAP, as these genes are associated with biologic pathways involved in the carcinogenesis of GBM and are therefore considered as novel potential therapeutic targets. Conclusions: Based on data-driven prioritization, we identified three potential therapeutic druggable targets, which have not yet been explored in the context of glioblastoma. Further preclinical and clinical research on the inhibition of these druggable genes is necessary and may lead to an improvement of treatment outcomes for patients with GBM.