bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic alteration features of six cancers and their correlation with clinical characters using the next generation sequencing.
Authors: Dong Qian , Yang Haiying , Jiang Da 
Published: May 2019

e13130 Background: Next-generation sequencing (NGS) examination based on liquid biopsy has been agreed as a kind of routine diagnostic tool in cancer field and may provide new sights about oncogenesis mechanisms. This study aimed to observe the genomic alteration features of common cancers and their correlation with clinical characters. Methods: We enrolled 39 subjects (38 subjects with cancer and 1 healthy subject) and administrated mutation examination using a panel including 38 genes, which targeted 6 cancer types. For each subject, the genomic DNA was extracted and NGS was performed. Results: All patients were found to carry at least one alteration among the 38 genes. PSM2 showed a highest mutation rate, with 77% subjects carrying mutations in this gene. Besides, MSH2 and STK11, etc. exhibited a high mutation rate. Overall 17 genes were found to contain known pathogenic or outcome-unknown mutations, among which 15 had outcome-unknown mutations and 5 had recognized pathogenic mutations. RAD50 had a highest frequency of outcome-unknown mutations, and secondly MLH1 and MRE11A. The clinical characters including sex, metastasis/recurrence, and family cancer history had relationships with mutation types. Conclusions: Genomic DNA sequencing is a feasible and minimally invasive approach in cancer genetic analysis and a promising tool in prediction of cancer onset and prognosis. A large amount of variations are associated with sex, family history and cancer types, and may decide metastasis/recurrence outcomes. Those who have a family history of cancer are recommended to receive NGS examination.
Screening of colorectal cancer (CRC) patients for lynch syndrome (LS) emphasizes the need for public insurance coverage of genetic testing: Results of a national program by the Hellenic Society of Medical Oncology (HeSMO).
Authors: Saridaki Zacharenia , Saloustros Emmanouil S. , Tsoukalas Nikolaos , Makatsoris Thomas , Lypas Georgios , Kalofonos Haralabos , Christopoulou Athina , Bompolaki Iliada , Sougklakos Ioannis , Voulgaris Evangelos , Karampeazis Athanasios , Papandreou Christos , Anagnostopoulos Athanasios , Galani Eleni P. , Ballasis Konstantinos , Zagouri Flora , Rizos Georgios , Athanasiadis Athanasios , Varthalitis Ioannis I. , Boukovinas Ioannis 
Published: May 2019

e13141 Background: Lynch Syndrome is associated with germline mutations in Mismatch Repair (MMR) genes ( MLH1, MSH2, MSH6, PMS2). CRC patients whose tumors exhibit high-level microsatellite instability (MSI-H) have an increased probability of LS. Although the diagnosis of LS has important implications for the patient and the family, germline genetic testing is not reimbursed by the Hellenic Public State Healthcare Services. To address this need HeSMO conducted a national program to screen and diagnose CRC patients with LS. Methods: All patients with CRC were eligible. Assessment for LS involved initially screening tumor tissue for the presence of MMR deficiency, either via molecular MSI testing or via immunohistochemistry (IHC) to detect the absence of one or more MMR proteins. Patients with an MMR-deficient tumor in the absence of a somatic cause (e.g. BRAF mutation or MLH1 promoter hypermethylation) underwent genetic counseling and germline testing to confirm a LS diagnosis. Results: From June 2017 to December 2018, 104 patients diagnosed with CRC were enrolled and tested. Median age of diagnosis was 58,5 years (range 32 - 89) and male-to-female ratio was 1.6:1. Fifty patients (48%) had tumors that exhibited the MSI-H phenotype. From the MSI-H tumors, 41 (82%) did not harbor the BRAF V600E mutation and 33 of them (80.5%) did not harbor an MLH1 promoter hypermethylation. Therefore, 33 patients were invited for genetic counseling and testing. Fifteen patients (45.45%) were diagnosed with LS: 6 ( 40 %) had a mutation in MLH1 (one of which had also a mutation in PMS2 gene), 4 (26.6%) in MSH6, 4 (26.6%) in MSH2 and 1 (6.6%) in PMS2. Conclusions: In our series, 30% of the CRC patients with MSI-H tumors were tested positive for LS. These results confirm the value of a universal screening program of CRC patients for LS. Hopefully, these results will convince the Hellenic Public State Healthcare Services to reimburse screening and germline genetic testing of CRC patients for LS.
Differences in MSI phenotype between cancer types using a new PCR-based pan-cancer biomarker panel.
Authors: Bacher Jeff , Udho Eshwar , Storts Doug , Halberg Richard , Galllinger Steven , Jenkins Mark A. , Lindor Noralane M. 
Published: May 2019

e13145 Background: A multiplexed biomarker panel was developed for detection of MSI that is more sensitive than currently available systems. Preliminary data showed an increased MSI sensitivity for colon polyps, endometrial (EC) and skin cancers. This study expands that finding to 14 different types of cancer. Methods: Selection of the best microsatellite markers was done using a cohort of 160 patients ≤55 years with ≥1 colon polyp and 100 EC patients ≤ 50 years. To validate the new panel, a cohort of 100 Lynch syndrome CRC, 100 sporadic MSI-High CRC, 100 sporadic MSI stable CRC and 219 extra-colonic cancers from the Colon Cancer Family Registry were tested for MSI. Samples were screened using a new 8-marker panel and Promega’s MSI Analysis System. Mismatch repair (MMR) gene mutation status and expression were determined. To compare the relative sensitivity of the 8-marker panel across all cancer types we developed a quantitative “MSI-score” for each cancer type. Results: Considerable differences in MSI phenotypes were observed between cancer types and a new approach to scoring MSI in extra-colonic cancers is proposed. Relative intensity of the MSI phenotype was characterized by MSI-Scores ranging from high of 66 (small intestine) to 6 (brain). The mutations in MSI samples were significantly more common and allele size shifts larger with the new biomarkers, making MSI classification more accurate and robost. MSI, IHC and MMR gene mutation status were highly correlated. Conclusions: The MSI sensitivity of the new biomarker panel for most cancer types was significantly higher than currently available PCR-based MSI systems. Development of the new pan-cancer PCR-based MSI system allows laboratories to leverage established equipment and known analysis techniques to keep turnaround time and costs, quick and affordable compared with emerging NGS-based technologies.
Towards a screening test for cancer by circulating DNA analysis.
Authors: Thierry Alain R. , Tanos Rita , Otandault Amaelle , Mollevi Caroline , Bauer Audrey , Tousch Geoffroy , Picque Lasorsa Laurence , El Messaoudi Safia , Colinge Jacques , Colombo Pierre-Emmanuel , Jacot William , Mazard Thibault , Sayagues Jose Maria , Gillet Brigitte , Pezet Denis , Ychou Marc 
Published: May 2019

e13146 Background: Following works on the clinical potentials of circulating DNA (cfDNA), our group is now particularly focused on evaluating its potential for early detection of cancer. We recently developed a test (MNR: Multi Normalized Ratio), based on various cfDNA parameters determined by a specific q-PCR based method, targeting both nuclear and mitochondrial sequences. When applied to the supernatant of cell culture, the MNR had a discriminative potential of 100% between normal and cancer cell lines. Methods: We recently developed a screening test (MNR: Multi Normalized Ratio), based on various cfDNA parameters determined by a specific q-PCR based method, targeting both nuclear and mitochondrial sequences. When applied to the supernatant of cell culture, the MNR had a discriminative potential of 100% between normal and cancer cell lines. Results: We are currently carrying out an extensive evaluation of this test in plasma samples from diagnosed and healthy individuals. Preliminary results on the plasma of 289 healthy subjects and 1,200 patients with various types of cancer (colorectal, breast, lung, liver, pancreatic, ovarian) of all stages, revealed a high potential with an AUC of 0.82 (0.78-0.84, 95% confidence interval, CI) and 70% sens. with 78% spe.. In breast cancer (N = 169), an AUC of 0.82 (0.78-0.86, 95% CI) with 72% sens. and 80% spe. were observed. In all stages CRC patients (N = 887), the results showed an AUC of 0.81 (0.78-0.84, 95%, CI) and 68% sens. with 80% spe.; for CRC stages 0/I/II (N = 249), an AUC of 0.75 (0.71-0.80, 95% CI) and 60% sens. with 79% spe.; and for CRC stage IV (N = 101), a 0.86 AUC (0.82-0.91, 95% CI) with 81% sens. and 78% spe.. When combining the MNR test to a threshold value of the total concentration of cfDNA (AUC = 0.82 (0.79-0.84, 95% CI), 70% sens. and 80% spe. in all stage cancers (N = 1078)), in CRC stages 0/I/II (N = 249) vs Healthy Individuals (N = 289), we observed a 63% sens. with 84% spe. Conclusions: Furthermore we recently discovered that cfDNA fragmentation, as determined by Whole Genome Sequencing using either double or single strand library, is also a parameter enabling discrimination between healthy and cancer individuals. Data on a multi-parametric test combining total cfDNA quantification, MNR and fragmentation biomarkers with help of a ongoing decision tree algorithm in machine learning will be presented during the meeting. Our on-going data suggest that our strategy in targeting cfDNA quantitative/structural features might be powerful for cancer screening/early detection and appears as an alternative or a synergistic combination to searching mutations.
The effect of the Affordable Care Act on genetic testing patterns and outcomes for inheritable cancer syndromes: A single institution experience.
Authors: Zhou Zhen Ni , Frey Melissa Kristen , Fields Jessica , Gordhandas Sushmita , Ruiz Maria Paula , Caputo Thomas A. , Holcomb Kevin , Chapman-Davis Eloise 
Published: May 2019

e13157 Background: National guidelines recommend genetic testing for women at increased risk for pathogenic mutations, however insurance coverage is a commonly cited barrier to test completion. The major provisions of the Affordable Care Act (ACA) became available in New York State (NYS) in January 2014. We sought to evaluate the effect of insurance status on genetic testing patterns following introduction of the ACA. Methods: Insurance status and genetic testing patterns at the hereditary breast and ovarian cancer center at a single institution were reviewed between 1/1/2013 and 12/31/2016. Insurance status and association with testing type and clinical outcomes were evaluated before and after January 2014. Results: During the study period, 1535 women underwent genetic counseling and genetic assessment. When comparing the cohort of women undergoing genetic testing prior to and following January 2014, significant increases in patients undergoing multigene panel testing were observed across all insurance types (6.3% vs. 40.6%, p < 0.001). While a significant increase in the number of patients with private insurance or Medicaid as primary coverage was seen, the increase in insured women was largely attributed to insurance polices through the ACA exchange (p < 0.001), with the majority being Medicaid ACA plans (80.3%). Conclusions: Since expansion of health insurance through the ACA in NYS, there has been a shift in the demographics of women undergoing genetic testing at a hereditary breast and ovarian cancer center with significantly more insured women and a rise in multigene panel testing. With insurance expansion and improved access to comprehensive genetic testing, insurance status should not be an obstacle for genetic testing.
Do genetic testing criteria identify individuals with Lynch syndrome prior to cancer diagnoses?
Authors: Reys Brian , Mauer Caitlin , Pirzadeh-Miller Sara , Ross Theodora S. 
Published: May 2019

e13158 Background: Screening colonoscopies every 1-2 years are estimated to decrease the risk for colorectal cancer (CRC) development in individuals with Lynch syndrome (LS) by 62-72%. However, in order for risk reduction to be effective, genetic testing guidelines must identify individuals with LS before they develop CRC. Current NCCN indications for LS evaluation focus on individuals who have already developed cancer. This study aims to identify the effectiveness of NCCN criteria in identifying LS patients before a cancer develops. Methods: A retrospective chart review was performed for 173 patients with a personal history of a LS-associated cancer seen at UT Southwestern and affiliate hospitals between 2009-2018. All patients tested positive (pathogenic or likely pathogenic) for a LS-associated mutation. Review determined if patients met NCCN (v1.2018) criteria for the evaluation of LS before and after their personal diagnosis of cancer. The study controlled for known mutations in families, past iterations of NCCN guidelines and instances of limited family history. Results: Of patients with LS, 31.8% (55/173) met NCCN testing criteria only after their personal diagnosis of cancer. Data per gene reveals 13.3% (8/60) MLH1, 25.4% (16/63) MSH2, 44.8% (13/29) MSH6 and 85.7% (18/21) PMS2 mutation carriers in the cohort were missed by current guidelines . Conclusions: 31.8% of patients with LS mutations would not have met NCCN LS evaluation criteria prior to their diagnosis of cancer. Criteria disproportionately missed individuals with lower penetrant MSH6/PMS2 mutations. These findings highlight a need for the field to develop criteria that support the detection of LS in individuals with and without cancer. As the field debates the merits of population based testing, this study suggests the current criteria for LS germline testing are not sufficient for identification of LS prior to cancer diagnosis for many patients with LS.
Pulmonary F-18 FDG uptake of non-tumor area in lung cancer patients to provide risk stratification in postoperative acute exacerbation of interstitial lung disease.
Authors: Yamamichi Takashi , Shimada Yoshihisa , Makino Yojiro , Kakihana Masatoshi , Kajiwara Naohiro , Ohira Tatsuo , Ikeda Norihiko 
Published: May 2019

e13165 Background: The incidence of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) is higher than the general population. In IPF patients with lung cancer, postoperative acute exacerbation (AE) is considered a fatal comorbidity. This study aimed to investigate whether FDG-PET/CT can be used to assess the risk of postoperative AE of IPF and severe respiratory adverse events (SRAE),which are defined as grade 3a or more severe respiratory complications such as AE, bacterial pneumonia, empyema, and bronchial fistula based upon Clavian-Dindo classification. Methods: We identified 822 patients with lung cancer who had preoperative FDG-PET/CT and subsequent pulmonary resection from July 2012 to July 2018. We reviewed the patients’ clinical records and transferredthe preoperative FDG-PET/CT images of each patient to SynapseVincent system (Fujifilm Corporation, Tokyo, Japan) for measuring SUV value of the lung.Inevery case, both SUVmax of main tumor (tumor-SUVmax) and non-lung tumor part (NLT-SUVmax) were measured. Univariate and multivariate analyses were performed for exploring significant parameters associated with AE and SRAE. Results: The cohort in this study consisted of 460 men and 362 women (mean age 67.9 ± 10.1 years; range 23–87). SRAE was observed in 35 (4.2%) patients including those with AE (n = 16, 1.9%). NLT-SUVmax and presence of IPF on CT were the independent predictive factors for both AE and SRAE. The receiver operating characteristic (ROC) area under the curve (AUC) of significant factors associated with AE and SRAE was measured, and cut-off levels on ROC curves for significant parameters associated with AE and SRAE were 1.69 and 1.55, respectively. The risk rates for the incidence of AE and SRAE according to NLT-SUVmax and chest CT findings were 19.0 % and 30.2% of the patients with positive IPF on CT and NLT-SUV max ≥1.69. Conclusions: NLT-SUVmax was the independent predictor of the incidence of AE and SRAE for patients who underwent pulmonary resection. FDG/PET-CT can be used in routine clinical practice to identify high-risk individuals for AE who require careful and intensive observation after pulmonary resection and that can facilitate clinical decision-making.
Risk factors associated with a second primary lung cancer (SPLC) in patients (pts) with a previous initial primary lung cancer (IPLC).
Authors: Nagasaka Misako , Farhat Dina , Belzer Kimberly , Kim Seongho , Mamdani Hirva , Sukari Ammar , Milczuk Mary Ann , Schwartz Ann G. , Wozniak Antoinette J. 
Published: May 2019

e13166 Background: The risk for development of a SPLC after treatment of an IPLC is around 1% to 2% per pt per year. The aim of this study was to characterize the risk factors associated with the development of a SPLC. Methods: Pts registered in the Karmanos Cancer Institute Tumor Registry diagnosed with an IPLC between 2000 and 2017 were included in this study. Pts with an IPLC who later developed a SPLC were matched for age, histology and stage to pts with an IPLC who did not develop a SPLC. SPLC was defined as a second lung cancer with a different pathology or if the same pathology, anatomically, molecularly, or chronologically distinct. Six variables including: stage at IPLC, histology, family history, surgery as a primary treatment for IPLC, and smoking history (determined by pack years, and continued tobacco use after first diagnosis) were reviewed. Logistic and Cox regression analyses were performed to determine the relationship of these characteristics with the development of a SPLC, and their association with overall survival (OS). Results: 121 pts with IPLC who later developed an SPLC were identified and compared to 120 pts with IPLC who did not develop a SPLC. Logistic analyses did not show that stage at first diagnosis, histology, family history, smoking history, and continued tobacco use after first diagnosis to be relevant for increased risk of SPLC. Pts who were primarily treated with surgical resection had a significantly higher probability of developing a SPLC (Odds Ratio: 0.24, 95% CI: 0.12 to 0.48, p < 0.001). Pts who did not have surgical resection as their primary mode of treatment for IPLC had a significantly higher risk of death than those who received surgical resection (HR 3.02, 95% CI: 1.99 to 4.57; p < 0.001). Conclusions: Based on our findings, pts who had surgical resection for an IPLC were found to have improved OS and a higher possibility of developing a SPLC. Stage at first diagnosis of IPLC, histology, family history, smoking history and continued use of tobacco after first diagnosis did not correlate with increased risk for SPLC. These results warrant further investigation and if confirmed could have an impact on surveillance recommendations post resection of initial lung cancers.
The clinical characteristic and prognostic factors of leptomeningeal metastasis in patients with non-small-cell lung cancer: A retrospective study from one single cancer institute.
Authors: Yan Weiwei , Yu Jinming 
Published: May 2019

e13502 Background: Leptomeningeal metastasis (LM) is a detrimental complication of advanced NSCLC, and the optimal therapeutic approach for LM patients is in shortage. The retrospective study was to investigate clinical features and prognostic factors of NSCLC patients with LM. Methods: We retrospectively reviewed the records of NSCLC patients with LM at the Shandong Cancer Hospital and Institute between July 2014 and March 2018. Identified cases had pathology-proven NSCLC with either positive CSF cytology or LM enhancement by MRI. Results: One hundred and thirty-six NSCLC patients (58 men, 78 women) with LM were enrolled in the retrospective study, median age was 55 years (range, 29–89 years). Fifty-one patients harbored EGFR mutations and ALK rearrangement was detected in six patients. Treatment for LM consisted of EGFR-TKIs alone in 11 patients, WBRT alone in 19 patients, Chemotherapy (ChT) alone in 12 patients, EGFR-TKIs plus WBRT in 30 patients, WBRT plus ChT in 25 patients, and EGFR-TKIs plus ChT in 24 patients. The median progression free survival (PFSLM) was 3.9 months (95% CI, 3.178-4.622) and the median overall survival (OSLM) was 9.8 months (95% CI,7.5-12.1). A multivariate analysis indicated that KPS ≥ 80 (HR = 0.592, 95% CI:0.369-0.95; p = 0.03) and EGFR-TKIs (HR = 0.507, 95% CI:0.283-0.908; p = 0.022) after LM diagnosis were independent favourable predictors of survival, whereas smoking (HR = 1.181, 95 % CI:1.009-3.246; p = 0.047) was an independent predictor of poor survival. Conclusions: Patients with good performance status, non-smokers and the administration of EGFR-TKIs might improve clinical outcomes in NSCLC patients with LM.
Lethality and mitotic activity of T98G glioblastoma cells under the influence of pulsed magnetic fields and ionizing radiation.
Authors: Popov Ivan A. , Shikhlyarova Alla I. , Kit Oleg I. , Rostorguev Eduard Evgenevich , Gusareva Marina A. , Timoshkina Natalya N. , Potemkin Dmitrii S. , Atmachidi Dmitriy P. , Rozenko Ludmila Ya. , Zinkovich Mikhail S. , Zhukova Galina V. 
Published: May 2019

e13511 Background: Development of alternative methods of non-invasive therapy in neurooncology is determined by the need to prevent the continued growth of glioblastoma and radiation-induced complications. Usage of electromagnetic influence for these reasons is determined by the oscillatory nature of intracellular processes and results of previous studies on the effect of weak electromagnetic radiation in tumor growth. The purpose of the study was to reveal the effect of a pulsed magnetic field (PMF) and ionizing radiation (IR) on human T98G glioblastoma cells. Methods: Human T98G glioblastoma cells were cultured in the RPMI-1640 medium (Biolot, Russia) supplemented with 10% fetal bovine serum (Thermo Scientific HyClone, USA). The culture was seeded in the Biofil plates (at least 8x105 cells per 3 mL of the medium), incubated (CB 150 Binder, Germany) and exposed to IR 10 Gy (TheratronEquinox-BestTheratronics) for 11.7 min. and/or PMF 15 mT or 300 mT with a sequence of frequencies 0.3-3.0-9.0 Hz for 7 min. (Neiro-MS/D by Neirosoft, Russia). The efficiency criteria were lethality and the mitotic activity of human T98G glioblastoma cells. Results: The highest cellular lethality was registered 3 hours (18.7 vs. 5.2% in controls, p≤0.05) and a day after IR exposure. PMF 15 or 300 mT alone increased lethality by 2.5-2.8 times compared to controls (p < 0.05). IR plus PMF (15 mT) did not caused increased lethality. At the same time, the most pronounced decrease in the mitotic activity a day after exposure (by 4.7 times, p < 0.05) was registered in PMF alone (15 mT). Conclusions: The inhibitory effect of PMF on the viability of human glioblastoma cells indicates the prospects for its use as an accompanying treatment in neurooncology.