bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interim analysis of the data of non-interventional study to determine the prevalence of EGFR mutations in advanced NSCLC Russian patients (ORTUS).
Authors: Laktionov Konstantin K. , Demidova Irina , Ageev Aleksandr , Breder Valeriy Vladimirovich , Grigoriev Pavel , Gordiev Marat , Gurina Liudmila , Ivanova Evgenia , Imianitov Evgenii , Kekeeva Tatiana , Kozlov Vadim , Prikhod'ko Viktor , Ragulin Yury , Sakaeva Dina , Statsenko Galina , Filippov Aleksandr , Filipenko Maxim , Khaylenko Viktor , Andreev Sergei , Karaseva Vera 
Published: May 2019

e13109 Background: There is a little information of correlation between EGFRm rate in cytology and plasma samples in Russian NSCLC population. The interim analysis of the study aimed to evaluate the prevalence and types of EGFR mutations in paired cytology and plasma samples in treatment-naive patients with advanced NSCLC. Methods: ORTUS is a multicenter, non-interventional, prospective study to determine EGFR mutations rate in treatmentnaive Russian patients with advanced NSCLC. ClinicalTrials.gov identifier: NCT02321046. The study enrolled 426 patients in stage IIIB / IV of NSCLC. Interim analysis covered the data of 214 cytology verified patients (mean age - 62.6 (range 32-86) years, 58,4% of men) with EGFRm test results in paired cytology and ctDNA samples. 99.5% cases were adenocarcinoma. The proportion of non-smokers/smokers/exsmokers was 46.3%/36%/17.8% respectively. Stage IV disease was in 81% of cases; 84.1% of patients had symptoms. DNA isolation performed using QIAamp DNA FFPE Tissue Kit for cytology and Qiagen Circulating Nucleic Acid Kit for ctDNA according to the manufacturer’s instructions. EGFR gene mutations were analyzed using THerascreen RGQ EGFR PCR Kit in cytology samples and RGQ Plasma EGFR PCR kit in plasma (Qiagen). Results: EGFRm was identified in 17,8% cytology samples (38/214) that is close to 20,2% (1759/8716) in Russian tissue EGFRm study (Imyanitov et al., 2016). 10,3% of paired ctDNA samples were EGFRm positive. Sensitivity and specificity for ctDNA were 42.1%, and 97.1% respectively. The EGFRm rate was 3,9% and 2,6% in smokers, 5,3% and 0% in ex-smokers and 33,3% and 21,2% in nonsmokers in cytology and plasma samples respectively. EGFRm rate and concordance between cytology and ctDNA are presented in a table. EGFRm in ctDNA were detected more frequently in M1a/b groups (p = 0,028). Conclusions: Cytology samples are appropriate for EGFRm testing in NSCLC patients in comparison with tumor tissue ones. High tumor burden (positive metastatic status) is an important factor for successful mutation analysis in ctDNA. [Table: see text]
A retrospective study of mortality among teenage and young adult (TYA) cancer patients in India.
Authors: Chitalkar Prakash , Punia Ankur , Punia Anushree , Yadlapalli C Deepak 
Published: May 2019

e13110 Background: TYAs are a unique group struggling with cancer but also with personal transitions of life. Outcomes of cancer in this group are poorly reported as most reports either address pediatric or adult patients. We evaluated mortality among TYA cancer retrospectively to better understand their journey with cancer. Methods: Teenage and Young adults (15 – 29 years) , from four institutes were included in the retrospective study for the year 2017. Eight hundred and seven of 1310 patients with cancer diagnoses or caregivers were telephonically contacted, in a predefined questionnaire including questions on mortality. Results: Three hundred seventy-two (46.1%) of 807 TYA cancer patients died . Distance and time travel to hospital, demography and alternative medicine were a significant factor for increased mortality. Gender and the age epochs within the TYA group did not determine mortality. One hundred and sixty-two patients died while on treatment whereas 136 patients died while not on any treatment. Seventy-four patients died at disease relapse. Those who died of cancer survived for a median of 180 days (5 - 2340 days). One hundred and four patients (12.9%) died within 90 days of diagnosis.There were significantly more deaths ( 30.4%) in patients who abandoned treatment, than among patients who went on therapy ( 18.6%). ( p 0.0001). Conclusions: Mortality among TYAs with cancer in India is high and is determined largely by factors like demography and logistics.
Prevalence and clinicopathological factors of the EGFR mutation status of Vietnamese non-small cell lung cancer patients.
Authors: Mai Khoa Trong , Pham Cam Phuong , Nguyen LUNG TIEN , Vo Quynh Thi Thuy , Anh Nguyen TUAN , Binh Nguyen HUY , Hien NGO Thi Thu , Loi Nguyen Thuan , Dinh Ha Tran 
Published: May 2019

e13120 Background: To determine the epidermal growth factor receptor ( EGFR) mutation status in non-small cell lung cancer (NSCLC) patients in Vietnamese population at Bach Mai Hospital, and relation of different variables to the frequency of EGFR mutations. Methods: The EGFR mutation status of 1451 tissue samples in NSCLC patients and correlation among different variables of age, gender, smoking habit and histology groups were evaluated. Results: A total of EGFR mutation analysis was performed, with an overall mutation rate of 40.7%. The most prevalent categories were in-frame deletions in exon 19 (57.2% of the overall mutations); followed by L858R and L861Q in exon 21 (35.7%); exon 18 (4,6%); double mutation: 2.9%; The T790M mutation in exon 20 represented approximately 2.5%; The pooled prevalence of EGFR mutation was higher in female (60.6%), non-smokers (61.1%), and patients with adenocarcinoma (42.2%). Conclusions: The prevalence of EGFR mutations of NSCLC in Vietnam is higher than that in the West, but comparably equal to that in some Asian countries. It is associated with female sex, non-smoker status, and adenocarcinoma, sample tissue type and age, but not depends on disease stage and tumor sampling.
Co-occurring genetic alterations and primary EGFR T790M mutations detected by next-generation sequencing in pre-TKI treated patients with non-small cell lung cancer.
Authors: Tang Yuan , Wei Bing , Yu Yang , Gao Yun , Che Nanying , Shi Huaiyin , Fu Shijun , Gao Min , Lin Dongmei , Ma Jie 
Published: May 2019

e13128 Background: With the development of targeted drugs, there are more therapeutic options for patients with non-small cell lung cancer (NSCLC) harboring corresponding genetic alterations. However, cancers are frequently caused by alterations on multiple genes, which collaborate to promote tumor development. Methods: A total of 1353 NSCLC patients from five different clinical institutions were enrolled in this study. Concurrent DNA and RNA NGS analysis was performed using the Ion Ampliseq Colon and Lung Cancer gene panel v2 and the AmpliSeq RNA Lung Cancer Research Fusion Panel using FFPE samples from surgically resected NSCLC tumors. Results: Of the 1293 mutations that were detected, 2338 variants were identified in 24 genes, while 27 of the tumor samples were identified to have co-occurring DNA mutations (including insertions, deletions and point mutations) and RNA fusion mutations. Analysis of the 975 patients with EGFR-gene mutations revealed that the incidence of dual EGFR L858R/T790M mutations were higher compared to EGFR 19del/T790M, and the MAF of T790M was lower compared to 19del in dual EGFR 19del/T790M patients. Conclusions: Even with the non-random cohort of patients in this study, the genetic alterations detected in this study had a certain degree of representation of NSCLC (especially lung adenocarcinoma) in the Chinese population. The differences in the MAF of EGFR T790M may determine different responses to TKI therapy in patients harboring dual mutations.
Use of computer algorithms in the electronic health record to identify and triage primary care patients for hereditary evaluation.
Authors: Kohlmann Wendy , Tobik Katie , Flynn Michael , Hess Rachel , Weir Charlene R , Bradshaw Richard L , Del Fiol Guilherme , Kawamoto Kensaku , Schiffman Joshua David 
Published: May 2019

e13137 Background: Identifying individuals with inherited cancer susceptibility is critical for optimal cancer prevention and screening. Family history is a significant predictor of inherited risk. Algorithms to extract and analyze family histories in electronic health records (EHRs) provide an opportunity for enhanced identification. Methods: Algorithms were developed to screen existing family history information in the EHR and identify patients meeting genetic evaluation guidelines for hereditary breast, ovarian, and/or colorectal cancer. In a pilot implementation, the patients of 5 primary care physicians at 2 community clinics were screened with the algorithms. Patients for genetic counseling were notified through the patient portal or mail. Follow-up phone calls were made to non-responders. Results: The algorithms identified 40 patients meeting criteria. Fifteen (38%) scheduled an appointment, 9 (22%) declined/will think about it, and 16 (40%) did not respond and were unable to be reached by phone. To date, 9 patients completed appointments. The family history used by the algorithm was accurate in 8 of 9 cases. For one case, the EHR family history was for adoptive relatives. Six of the 9 patients had additional family history not in the EHR, including 2 patients at-risk for familial mutations in ATM and ACVRL1. Patients who responded had their last visit within the healthcare system an average of 0.25 years ago versus 1.13 years for non-responders (p = 0.0002). Conclusions: Algorithms for screening existing family history in the EHR can identify primary care patients for hereditary cancer evaluation. While this approach has a low rate of false positives, it will likely miss appropriate individuals as 78% of patients had incomplete EHR-based family history as compared to a gold-standard genetic counselor obtained pedigree. However, use of automated algorithms will allow healthcare system to begin offering genetic services to those who can be identified. Ongoing efforts include use of natural language processing to extract family history from narrative data and use of a standards-based approach for replicability across EHRs.
An optimized workflow for a fast molecular diagnosis of non-small cell lung cancer.
Authors: Wei Bing , Li Jun , Ren Pengfei , Chang Yuxi , Zhao Chengzhi , Xia Qingxin , Groen Harry J.M. , Ma Jie , Guo Yongjun 
Published: May 2019

e13139 Background: Lung cancer is the most common and lethal malignancy throughout the world, in which non-small cell lung cancer (NSCLC) is the dominant subtype. To distinguish between different cell types of NSCLC, i.e. adenocarcinoma or squamous cell carcinoma, the morphologic features of cancer cells are important, as well as specific molecular markers, i.e. TTF1, p63 and p40. Genomic studies have revealed different genetic aberrations between specific subtypes of NSCLC, and distinct response to targeted therapy. Therefore, molecular testing is essential for precision diagnosis and personalized treatment. The canonical workflow from diagnosis to next generation sequencing (NGS) tests needs about two weeks. Importantly, sometimes the residue material left after diagnostic staining may not be enough for NGS tests. This means a secondary biopsy is needed, which is not patient friendly. Methods: We optimized the canonical workflow by using BIOCO, a magnetic collector attached to microtome knife holder that can collect the abandoned tissue during slicing FFPE blocks. Therefore, the material used for NGS test was collected simultaneous during slicing for pathological diagnosis. In total 123 FFPE tumor blocks from suspicious NSCLC patients were included to evaluate: 1. how long it will take from diagnosis to make treatment decision? 2. If the material collected by BIOCO is sufficient for NGS test and whether the result can be trusted. Results: 1. The BIOCO workflow only needs 7 days for the diagnosis and making therapeutic plan. 2. The BIOCO could collect enough FFPE tissue for NGS test even with HE, IHC stanning and FISH test for all the samples; however, 14 samples failed NGS test because of insufficient material left following the canonical workflow. 3. the detection sensitivity and specificity of the BIOCO method are comparable with the canonical workflow, with a consistence of 94.9%. Conclusions: Here we propose an optimized workflow by using the BIOCO collector we invented, which shortens the canonical workflow from two weeks to one week, and it fully utilizes the limited biopsy tissue for NGS testing so that the secondary biopsies are avoided.
Germline genetic testing in ovarian cancer patients: Identifying barriers to care and opportunities for improvement.
Authors: Stock Elizabeth , Cowan Matthew , Romero Iris L , Yamada Seiko Diane 
Published: May 2019

e13142 Background: Despite recommendations that all patients with non-mucinous high grade epithelial ovarian cancer (EOC) undergo germline genetic testing, only 10-15% of patients nationwide are tested. The aim of this study was to determine the rate of genetic testing at a single academic institution, identify patient characteristics associated with undergoing testing and improve delivery of care by identifying barriers to testing. Methods: An IRB-approved single institution ovarian cancer database was used to identify patients with non-mucinous high grade EOC treated between 1996 and 2017. The rate of genetic testing was calculated and the referral and testing process was mapped. Patient demographics, clinical characteristics and family history was obtained from the medical record. Univariate and multivariate logistic regression was performed. Results: From 1996 to 2017, 588 patients were treated for non-mucinous EOC. Of those, 200 patients (34%) were referred for genetic counseling and 175 (30%) were tested. Younger patients were more likely to undergo testing. Fewer African Americans had genetic testing than Caucasians (18% vs 33%, p = 0.003) and patients with public insurance were less likely to undergo testing compared to those with private insurance (23% vs 34%, p = 0.005). Patients with recurrent disease were less likely to undergo testing but rates did not vary by cancer stage or histology. A family history of cancer was the most significant predictor (43% vs 11%, OR = 5.85, p < 0.001). For patients diagnosed in the past 5 years, the testing rate improved to 57.9%. When the referral and testing process was mapped, a complex internal referral system was revealed. Barriers to testing included provider awareness, additional patient visits, patient preference and insurance coverage. Conclusions: Rates of germline genetic testing for patients with ovarian cancer have increased over time as guidelines for genetic testing have evolved, however, over two thirds of patients were not tested and African Americans were less likely to be tested. These findings support increasing provider education and patient counseling, testing directly in the gyn/oncology office and consideration for instituting a Traceback program.
Combinational analysis of IDH1/IDH2 mutations, 1p/19q deletions and MGMT promoter methylation for molecular testing of glioma.
Authors: Zhang Xiaoni , Qu Hongyue , Yang Qing , Zhu Ziyang , Huang Tanxiao , Chen Shifu , Edwards Jeremy , Xu Mingyan 
Published: May 2019

e13152 Background: Mutations in IDH1 and IDH2, co-deletion of 1p and 19q, and the hyper methylation of the MGMT promoter are the most reported genetic alterations in glioma tumors. Therefore, we designed a study to analyze the prevalence of these biomarkers in glioma, and the correlation of these biomarkers with diagnosis and prognosis. Methods: From September 2018 to January 2019, eighteen patients with primary glioma were prospectively enrolled. For each patient, freshly frozen tissue or FFPE samples were collected. DNA was extracted from these samples and sequenced to at least 5,000× coverage. IDH1/IDH2 mutations and 1p/19q deletions were detected from the sequencing data, whereas MGMT promoter methylation was evaluated by real-time fluorescence qPCR. Results: Of the eighteen patients, 44.4%(8/18) and 33.3%(6/18) harbored IDH1 /IDH2 mutations and 1p/19q deletions, respectively, and 72.2%(13/18) contained MGMT promoter hyper methylation. Within these patients, we found a correlation between IDH1/IDH2 mutation and 1p/19q deletion. Namely, among the 8 patients with a IDH1/IDH2 mutation, 75%(6/8) also contained a 1p/19q deletion, whereas none of the 10 patients with wide-type IDH1/IDH2 displayed the 1p/19q deletion. There was also a correlation between mutations at the loci and MGMT promoter hyper-methylation, specifically, 87.5%(7/8) of the patients with IDH1/IDH2 mutations also exhibited hyper-methylation in MGMT, whereas only hyper-methylation was observed in only 40% (4/10) of IDH1/IDH2 negative patients. Conclusions: From our preliminary result, IDH1/IDH2 mutations may be associated with 1p/19q deletion. To further verify this result, a larger, longitudinal study is ongoing at our institution.
Early non-invasive detection of stage Ia lung cancer using circulating tumor DNA methylation haplotypes (ctmDNA) in plasma.
Authors: Zhang Kun , Wang Zhoufeng , Li Zhe , Lu Jingyi , Min Jun , Gore Athurva Jayavant , Gole Jeffrey , Liu Rui , Gao Yuan , Li Weimin 
Published: May 2019

e13159 Background: Lung cancer is one of the most common forms of cancer and is responsible for approximately 1.8 million deaths per year worldwide. The current 5-year survival rate for lung cancer is only 18%; however, this improves to 56% if the cancer is detected early. While low-dose CT scans have shown promise as an early detection method, only 16% of lung cancer is currently detected at an early stage. We therefore set out to develop a non-invasive blood-based screening assay to identify lung cancer at an early stage using ctmDNA (circulating tumor methylated DNA haplotypes). Methods: Blood samples were prospectively collected from two partner hospitals from 325 healthy individuals and 116 individuals diagnosed with lung nodules by low-dose CT scan in EDTA or Streck BCT tubes and immediately separated into plasma. Patients with lung nodules that appeared cancerous then underwent surgical resection, and cancer diagnosis was confirmed via pathology. Patients were matched between healthy and cancer groups by age, sex, and smoking status. Plasma samples were processed using the Singlera Genomics LUNA assay, a targeted bisulfite sequencing method which identifies methylation haplotype patterns related to early-stage lung cancer. 241 samples were used to train a classification model based on pathology results, and 200 samples were used as a test set to validate the model. Results: In the independent test set, the LUNA assay was able to show a sensitivity of 91.9% to detect early-stage lung cancer with a specificity of 93.3% in healthy patients. Even patients with stage Ia lung cancer were readily detected by the LUNA assay (sensitivity of 91.7%). Conclusions: We have shown that ctmDNA can be utilized to non-invasively screen for early-stage lung cancer with high sensitivity and specificity, paving the way for a blood-based lung cancer early screening assay.
DNA Input, sequencing depth, and maximum somatic allele frequency may affect the concordance between blood TMB and tumor TMB.
Authors: Huang Yuqing , Liu Qiang , Min Xianjun , Yang Yingshun , Pei Guotian , Wang Shuai , Wang Xiaoyu , Li Hui , Zhang Xiaoni , Qu Hongyue , Wen Mingxin , Chen Yaru , Edwards Jeremy , Chen Shifu , Wang Jun 
Published: May 2019

e13163 Background: Tumor mutation burden (TMB) is recognized as a promising biomarker for PD-1/PD-L1 blockade therapy. However, a tissue biopsy is often not available, and hence a liquid biopsy using blood can be used to evaluate TMB (which is known as blood TMB). Unfortunately, the concordance of blood TMB (bTMB) and tissue TMB (tTMB) is not stable, and may be affected by the sample preparation methodology and sequencing depth. Therefore, e designed a study to explore the factors, which may significantly impact the concordance between bTMB and tTMB. Methods: From September 2018 to January 2019, 98 patients with pan-cancer were prospectively enrolled. For each patient, a tissue sample and paired plasma sample were collected. These samples were sequenced using a custom 605 cancer specificgene panel. Results: The data indicated that bTMB and tTMB were correlated, but the DNA input, sequencing depth and maximum somatic allele frequency (MSAF) might affect their concordance. The Spearman’s rank correlation (SRC) between bTMB and tTMB of 38 patients with > = 25ng cfDNA vs. 60 patients with < 25ng cfDNA was 0.77 vs. 0.15, respectively. Additionally, we explored the impact of sequencing depth and determined that the SRC (between bTMB and tTMB) of 25 patients with a sequencing depth > = 2,500x vs. 73 patients with a sequencing depth < 2,500x was 0.74 vs. 0.28, respectively. Finally, we showed that the allele frequency was critically important as well. We determined that the SRC (between bTMB and tTMB) of 50 patients with cfDNA MSAF > = 1% vs. 48 patients with cfDNA < 1% was 0.71 vs. -0.03. Conclusions: To improve concordance between bTMB and tTMB for better predicting efficacy of immunotherapy, we recommend that cfDNA input should be more than 25ng, and average effective sequencing depth should be higher than 2,500x, and the correlation hold for an allele frequency treating than 1%.
De novo malignancy in recipients of solid organ transplant from donors with intracranial cancer.
Authors: Carsky Katie , Carr Christopher , Werner Cassidy , Khadra Helmi , Hamner John Blair , Paramesh Anil S , Dumont Aaron S 
Published: May 2019

e13507 Background: In 2016, 33,610 organ transplants were performed in the US. Nevertheless, there is a critical deficiency of available organs. Currently, malignant neoplasms in the donor preclude organ donation, with some exceptions, such as certain CNS tumors without metastatic disease. The literature illustrates the risk of CNS tumor transmission with organ transplantation as 0-3% in the absence of additional risk factors, but organs from fewer than 0.5% of the 13,000 patients that die of glioma annually are procured. Given the critical need, we sought to reaffirm the safety of organs from donors with intracranial cancer by examining de novo malignancy outcomes in a large dataset. Methods: We examined the UNOS database to determine whether recipients of solid organ transplant from donors with intracranial cancer were at increased risk of de novo malignancy. Included were 119,430 subjects ages 18 to 65 who underwent heart, heart and lung, intestine, kidney, kidney and pancreas, liver, lung, or pancreas transplant from 1987 to 2012 and for whom there was complete data on donor history of intracranial cancer. 2-by-2 contingency tables were used to calculate odds ratios of exposure to donors with intracranial cancer. Outcomes included five-year survival, composite development of any malignancy, and development of specific malignancies including melanoma, esophageal, stomach, small intestine, pancreas, larynx, mouth, colorectal, primary liver tumor, and metastasis to liver. A p value of ≤ 0.05 was statistically significant. Results: 718 (0.60%) organs came from donors with intracranial cancer. 437 (79.02%) recipients of organs from donors with intracranial cancer survived 5 years, versus 71,055 (77.64%) recipients of organs from donors without intracranial cancer (p = 0.47). 113 (15.74%) recipients of organs from donors with intracranial cancer developed de novo malignancy, versus 17,963 (15.13%) recipients of organs from donors without intracranial cancer (p = 0.60). Of 17 contingency analyses of development of specific malignancies, we detected only 1 statistically significant positive association, de novo colorectal cancer in recipients of solid organ transplant from donors with intracranial cancer (p = 0.048, OR = 2.56). Given the large number of analyses and marginal significance of this in a very large dataset, it is likely type I error. Conclusions: Metastasis of primary CNS tumors beyond the CNS is a rare occurrence without additional risk factors. With the current organ shortage, donors with primary CNS malignancy are ideal candidates for organ donation.