bluuebunny/crossref_metadata_2025_split huggingface dataset:
The landscape of palliative systemic therapy and overall survival of 2,063 advanced breast cancer patients in the China National Cancer Center.
Authors: Guan Xiuwen , Xu Binghe , Ma Fei , Li Qing , Zhang Pin , Yuan Peng , Wang Jiayu , Luo Yang , Cai Ruigang , Li Qiao , Mo Hongnan , Li Yiqun , Lin Shaoyan , Chen Yimeng , Wang Zijing 
Published: May 2019

e12583 Background: Despite novel therapeutic options evolved rapidly, advanced breast cancer (ABC) remains an incurable disease with a median overall survival (OS) of 24-30 months. However, real-world data on the treatment and outcome of ABC in routine practice was rare, especially in Chinese cohort. Methods: We summarized the clinicopathological characteristics, therapeutic regimens and survival outcome of 2063 females with ABC who were hospitalized between January 2003 and December 2013 from the Database in China National Cancer Center. Results: The median OS of enrolled population was 42.6 months (95% CI 39.6 to 45.5). Significantly prolonged OS was observed since 2011 ( P= 0.041), with a median OS of 41.0 months (95% CI 37.5 to 44.4) in patients diagnosed with ABC in 2003-2010 and 44.6 months (95% CI 37.9 to 51.2) in 2011-2013, respectively. Between these two periods, Luminal-like, HER2-positive, and Triple-negative patients had an improved median OS of 45.9 to 56.2 months ( P= 0.001), 38.3 to 43.1 months ( P= 0.414), and 28.6 to 28.7 months ( P= 0.364), respectively. As for the analysis of therapeutic mode alteration, the proportion of multidisciplinary care for recurrent disease raised significantly over the years (χ2= 8.2, P= 0.004), from 39.6% in 2003-2010 to 47.7% in 2011-2013. In Luminal-like patients, the application of endocrine therapy increased significantly from 64.4% in 2003-2010 to 77.6% in 2011-2013 during the palliative systemic therapy (χ2= 17.7, P < 0.001). Among HER2-positive patients, significantly increased application of HER2-targeted therapy were observed in both adjuvant therapy (χ2= 4.7, P= 0.030) and palliative therapy (χ2= 10.3, P= 0.001) between these two periods. For patients receiving the first-line chemotherapy, the use of maintenance treatment ascended dramatically from 37.1% in 2003-2010 to 58.8% in 2011-2013 (χ2= 50.5, P < 0.001). The percentage of participating clinical trials was 14.3%, slightly increased in 2011-2013, when compared with the proportion of 11.6% in 2003-2010 (χ2= 2.0, P= 0.160). Conclusions: Real-world data revealed that significantly prolonged OS in China was achieved since 2011 due to the increased use of multidisciplinary care, endocrine therapy, HER2-targeted therapy and maintenance treatment.
Nab-paсlitaxel (Nab-P) in patients with metastatic breast cancer (mBC) with visceral crisis (VC): Efficacy and tolerability.
Authors: Novoselova Kristina A. , Vladimirova Liubov Yu , Abramova Natalia A , Storozhakova Anna E , Popova Irina L. , Tikhanovskaya Natalia M. , Ryadinskaya Ludmila A. , Lyanova Aza A. , Salamov Georgy , Teplyakova Maria , Prikhodko Ekaterina , Tishina Anna V. 
Published: May 2019

e12589 Background: Better efficiency and safety of Nab-P is known to be due to the advantages of pharmacokinetics and pharmacodynamics of the drug. The fraction of unbound paclitaxel in plasma is 2.6-fold higher with Nab-P than with P. The purpose of the study was to assess efficacy and safety of Nab-P in ≥2nd lines of chemotherapy (CT) in patients (pts) with mBC with VC. Methods: Inclusion criteria: mBC with VC, ≥ 2 line of CT, HR+, HER2neu+ or triple negative type (TN), normal liver and renal function. Pts received Nab-P 260 mg/m2 q 21 days. Pts with Her2/Neu + received trastuzumab 6 mg/kg q 21 days. Results: 32 mBC pts, mean age 51.34 years (CI 35-76) were included. Among 32 pts Her2/Neu + had 5 (15.6%), TN – 9 (28.1%), HR+ 18(56.3%). 13(40.6%) pts received Nab-P as 2 line of CT, 13 (40.6%) pts, as 3-4 lines, 7(21.9%) as ≥5 lines. Pts were divided into 2 groups: group A - pts with VC 17(53.1%), group B - without VC 15(46.9%). Groups were comparable by age, number of previous CT lines, immunohistochemical types of BC. Group A had 2.47±0.32 CT lines (CV51.83%), including 8(47%) pts, who had received paclitaxel (P) in previous CT lines. Group B had on average 2±0.27 CT lines (CV53.03%). The objective response rate (ORR) was 37.5%(12 pts). In the group A ORR was 35.3% (6 pts). Out of 8 pts with VC, who had received P in previous lines, ORR was achieved in 3 pts (37.5%). In the group B ORR was 33.34%(5 pts). TTP was 6.8 mos (95% CI 6.1-13.7) for all pts, in the group A – 5.7 mos (95% CI 5.9-10.2), in the group B 6 mos (95% CI 6.5-13.7) (p = 0.046). Median 3-year OS of pts in group A was 18.9 mos (95% CI 4.3-22.4), in group B - 22.5 mos (95% CI 8.2-26.7) (p = 0.038). Toxicity did not differ significantly in pts in groups A and B and was manageable. Pts, who previously received P, had no new or severe toxicity. Conclusions: The data obtained confirms the possibility of Nab-P application in pts with VC. The use of Nab-P in pts treated with taxanes in previous lines is supposed for further study.
An EGFR extracellular domain mutation data in the East Asian non-small cell lung cancer populations and response to icotinib: A multicenter study.
Authors: Wang Wen xian , Xu Chunwei , Chen Yu , Cai Xiuyu , Fang Yong , Zhang Quxia , Zhu You-cai , Yu Zongyang , Chen Gang , Wang Hong , Zhuang Wu , Chen Xiaohui , Huang Yun-jian , Shen Hong , Zheng Song , Zhou Ji'an , Ye Junhui , Fang Meiyu , Lv Tangfeng , Song Yong 
Published: May 2019

e13000 Background: “Pan-negative” non-small cell lung cancer (NSCLC) patient specimens that lack mutations in known targetable genes. EGFR extracellular domain mutations (ECD) as novel oncogenic mutations are found in colorectal cancer, glioma, and neuroblastoma cases and has not yet reported in NSCLC. No enough evidence between icotinib treatment and ECD has been reported in NSCLC. Methods: Comprehensive mutational analyses were performed on 3279 NSCLC specimens. In this cohort of patients, common lung cancer oncogenic driver mutations were firstly detected in EGFR, as well as the KRAS, BRAF, ALK, ROS1 and RET genes by next generation sequencing tumor DNA (ctDNA) and apply icotinib for treatment for EGFR ECD. Results: Of this entire cohort, sixteen (0.49%) patients (3279 cases) were identified with EGFR ECD, including p.L62R (2), p.R98Q (1), p.I213M (1), p.A237F (1), p.A289V (1), p.A289T (1), p.T302H (1), p.T354K (1), p.T363N (1), p.D368Y (1), p.T430S (1), p.A508V (1), p.N528D (1), p.K593Q (1) and G598V (1). During the treatment by icotinib, two cases (p.A289V, p.A289T) had partial response to icotinib for four and six months, which suggested that icotinib conferred sensitivity to A289X mutation. EGFR A289X mutations were sensitive to icotinib treatment in BaF3 cell lines and in xenograft models. These results paralleled those seen with the well-described EGFR oncogenic driver mutation, L858R, suggesting similar mechanistic underpinnings for the mutations. Conclusions: Here, a new EGFR driver mutation, A289X, was identified in the ECD of two NSCLC specimens. NGS may expand the EGFR mutations spectrum for icotinib treatment in NSCLC, however, it needs to be confirmed in more patients with NSCLC in East Asian and other populations.
Real-world large-scale study of ERBB2 gene fusions and its response to afatinib in Chinese non-small cell lung cancer (NSCLC): A multicenter study.
Authors: Xu Chunwei , Wang Wen xian , Zhang Quxia , Chen Yu , Cai Xiuyu , Fang Yong , Zhu You-cai , Huang Yun-jian , Wang Hong , Zhuang Wu , Zhang Yinbin , Wang Liping , Jiang Xiaofang , Cai Shangli , Huang Jianhui , Feng Shuitu , Fang Meiyu , Chen Gang , Lv Tangfeng , Song Yong 
Published: May 2019

e13002 Background: ERBB2 mutation has been found to be an oncogenic driver gene in non-small cell lung cancers (NSCLC) and ERBB2-directed therapies have shown promising results in this unique population, while little is known about ERBB2 fusion association with outcomes of afatinib. The aim of this study was to investigate the efficacy of afatinib in patients with advanced ERBB2 fusion NSCLC. Methods: A multicenter study in China was initiated from February 2014, and NSCLC patients have been enrolled as of December 2018. To determine the frequency of the ERBB2 fusions in NSCLC and other tumors, we analyzed data from 2743 clinical NSCLC cases, each of which had results from next-generation sequencing (NGS)-based 381 genes panel assay, analogous to the index patient. Results: Of this entire cohort, eight (0.29%) patients were identified with an ERBB2 fusion, including TNS4-ERBB2 (1), ERBB2-CD79B (1), IGFBP4-ERBB2 (1), ERBB2-PSMD3 (1), SEZ6-ERBB2 (1), ERBB2-PGAP3 (1), ARL5C-ERBB2 (1) and B3GNTL1-ERBB2 (1). The genes most frequently co-altered in patients with ERBB2 fusions were TP53 (37.50%), CDKN2A (25.00%), RB1 (25.00%) and RBM10 (25.00%). Overall TMB in the ERBB2 fusions was low (median 2.97 mut/Mb). For treatments, 25.00% patients chose afatinib, another patients chose chemotherapy or chemoradiotherapy, and case examples of advanced ERBB2 fusion driven NSCLC patients responding to afatinib were actively being sought thru our database. Conclusions: Patients with advanced ERBB2 fusion NSCLC showed a good outcome of afatinib compared to those with ALK/ ROS1 fusion which response to crizotinib, which strengthen the need for effective ERBB2-targeted drugs in clinical practice.
Improving access to genetic counseling services in an adolescent and young adult (AYA) clinic.
Authors: Ross Jessica , Bell Donna , Yarbrough Angela R. , Peterson Susan K. , Makhnoon Sukh , Arun Banu , Livingston J Andrew , Roth Michael 
Published: May 2019

e13009 Background: Numerous studies have explored genetic testing access and benefits in adult and pediatric cancer patients, however little is known about the use of these services in adolescents and young adult (AYA) cancer patients. Routine genetic counseling may be particularly important for AYAs who are survivors of childhood cancer, as 8.5% of children with cancer have an inherited pathogenic germline variant. Genetic testing also helps reduce cancer morbidity and mortality in adolescents, as well as helps to guide cancer prevention strategies in family members. This study describes an innovative approach to fostering AYA patients’ access to genetic counseling services. Methods: AYA patients (ages 15-29) with a new or prior cancer diagnosis were referred to MD Anderson Cancer Center’s AYA multi-disciplinary clinic. Prior to their clinic visits, a genetic counselor reviewed relevant medical and family history information for patients seen from 7/12/18 through 1/11/19. For those at risk for a hereditary cancer syndrome, a recommendation for a genetic counseling referral was given to the AYA medical provider based on established guidelines, professional consensus, and clinical judgement guided by thorough literature reviews. Results: In total, 254 AYA patients’ charts were reviewed and 70 (27.6%) patients had histories that warranted a genetic counseling referral. Of these 70 patients, 53 (75.7%) were not previously seen by genetics. Of the 53 patients newly recommended to be referred, 29 (54.7%) had referrals placed. Of the 24 patients not referred, 17 did not attend their AYA visit, 5 refused the referral, and 2 were not referred for undetermined reasons. Of those referred, 10 completed genetic counseling, 14 are scheduled for counseling, 3 did not attend their appointment, and 2 had counseling at another institution. This process led to a 41.3% absolute increase in referrals to genetic counseling for those at risk for hereditary cancer syndromes. Conclusions: The described clinic workflow identified gaps in genetic referrals and showed an innovative approach to fostering AYA access to genetic services. This approach may be useful for other institutions interested in increasing access to genetic services for AYAs.
Pathogenic germline mutation hotspots in east Asian cancer genomes.
Authors: Shi Xiaoshun , Chen Allen Menglin , Huang Kailing , Zheng Zhouxia , Chen Zhuona , Young Sylvia , Zhang Jiexia , Dong Xiaoying , Liu Xiguang , Lu Di , Feng Siyang , Morahan Grant , Cai Kaican 
Published: May 2019

e13011 Background: To summarise the prevalence of pathogenic germline variants in East Asian cancer genomes and to develop an online resource and reference for genetic analysis of cancer susceptible germline mutation hotspots. Methods: We performed the most extensive investigation of germline mutations in East Asian cancer population based on publicly available data collected from multiple institutions over 1,600 patients with 15 cancer types. The pathogenic cancer susceptibility gene mutations were called by analyzing whole exome sequencing data generated from the normal control samples from the cancer patients deposited on the SRA database. Results: Compared with 9,435 East Asian controls in the gnomAD dataset, we identified pathogenic recurrent germline mutations based on our MaGiC analysis pipeline including quality controlled, filtration and annotation. More than 150 variants were found, and the top 3 hotspot mutations are TP53 in 5 types of cancer, BRCA2 in 3 types of cancer and PIK3CA in 4 types of cancer. The hotspot variants(same cancer predisposition gene set, but different pathogenic mutations) were of population difference in comparison with Caucasian population. Conclusions: Our work is the first comprehensive analysis of East Asian cancer predisposition germline mutations. It provides informative references for cancer genetic consulting and early prevention in more than 20% of world population. The update of our database covering larger populations and more cancer types is needed and still ongoing.
Integrated genomics-based approach to identify new therapeutic targets and cancer biomarkers for lung cancer.
Authors: Daigo Yataro , Takano Atsushi , Nakamura Yusuke 
Published: May 2019

e13019 Background: Because the number of lung cancer patients who show good response to standard therapies is still limited, development of new anti-cancer agents with minimum risk of adverse effects and highly sensitive molecular biomarkers is urgently required. Methods: We have been screening novel therapeutic targets and their companion biomarkers for lung cancer as follows; i) To identify up-regulated genes in lung cancers by the gene microarray analysis, ii) To verify the candidate genes for their low expression in normal organs, iii) To validate the clinicopathological significance of their protein expression by tissue microarray covering hundreds of lung cancers, and iv) To verify their function for the growth of lung cancer cells by siRNAs. Results: We identified dozens of candidate oncoproteins and selected a serine/threonine kinase LASK2 (lung cancer-associated kinase 2). Immunohistochemical analysis showed that strong LASK2 positivity was an independent prognostic factor for non-small cell lung cancer patients (P < 0.0001). Suppression of LASK2 expression by its siRNAs inhibited proliferation of lung cancer cells. Introduction of LASK2 in mammalian cells also enhanced cellular growth in vitro and in mice model. Induction of LASK2 appeared to increase the levels of phosphorylation of oncogenic signal proteins for lung cancer. The data indicate that LASK2 is a prognostic biomarker and therapeutic target for lung cancers. Conclusions: Integrated genomics-based approach could facilitate the development of new cancer biomarkers as well as therapeutic targets for small molecules, monoclonal antibodies, nucleic acid drugs, and immunotherapies.
Confirmation of germline variants identified by tumor testing: A population-based study.
Authors: Pender Alexandra , Karsan Aly , Yip Stephen , Bosdet Ian , Young Sean , Tucker Tracy , Schrader Kasmintan A , Sun Sophie 
Published: May 2019

e13021 Background: Multi-gene panel tumour testing (TT) has been available in British Columbia since mid-2016 for metastatic non-small cell lung cancer (NSCLC), colorectal cancer (CRC), melanoma (MEL), low-grade glioma (LGG), and gastro-intestinal stromal tumours (GIST). TT can detect somatic driver mutations and potential pathogenic germline variants (pPGVs) associated with hereditary cancer susceptibility. We reviewed the frequency of pPGVs identified by TT and examined referral rates to the Hereditary Cancer Program (HCP) for confirmatory germline testing (GT) and therapeutic implications of PGV findings. Methods: All patients (pts) undergoing TT testing from October 1, 2016 to December 31, 2018 were identified. Diagnosis, age, gender, family history and treatment data were obtained. TT was performed by next-generation sequencing for all/selected regions of the following genes: AKT1, ALK, BRAF, BRCA1, BRCA2, CCND1, CCND3, CIC, EGFR, ERBB2, ERBB3, FUBP1, HRAS, IDH1, IDH2, KIT, KRAS, MAP2K1, MET, NRAS, PDGFRA, PIK3CA, PTEN, ROS1, SDHA, SDHB, SDHC, SDHD. Results: Among 2937 TTs, pPGVs were identified in 83 pts (2.8%) [Table 1]. 50 pts (57%) were referred to HCP, 41 had germline testing, and 14 PGV were confirmed. PGVs were most commonly identified in BRCA1/2 and SDHA and these findings did not influence oncologic treatments. Conclusions: TT detected pPGVs in 2.8% of unselected pts with metastatic cancers. Among 41 pts undergoing germline testing, 34% who would not have otherwise met testing criteria, had a confirmed PGV. Referral rates were low due to lack of patient and clinician awareness and poor health status. Although PGV findings did not directly impact treatment, TT identified 14 new families with hereditary cancer who can benefit from early detection and screening. Future directions include expansion of TT to include additional hereditary cancer susceptibility genes and development of digital tools for pts and clinicians. [Table: see text]
Discussion on several problems between tumor-associated venous thrombosis and driving genes status.
Authors: Zhang Xue , Jiang Da , Yang Haiying , Zuo Jing , Jin Hui , Huang Fang 
Published: May 2019

e13022 Background: The study aimed to explore clinical correlation between venous thrombosis and driving genes status in cancer patients (pts). Methods: The clinical data of cancer pts from 2014 to 2018 in our hospital were collected to calculate the overall thrombosis rate, driving gene mutation rate, and thrombosis rate in pts with mutated driving genes. Pts were divided into mutation group and non-mutation group based on the driving gene mutation status. Khorana model was used to divide each group into three subgroups and the thrombosis rate of each subgroup was calculated. The diagnostic value of the Khorana model was calculated in the whole patient set and each group. The correlation between driving gene mutation status and thrombus status was also analyzed. Results: A total of 2049 pts were enrolled, with 4.44% overall thrombosis rate and 72.13% driving gene mutation rate. The thrombosis rates in pts with EGFR, c-Met, ALK, HER-2, KRAS or ROS1 mutations were, in turn, 5.34%, 4.33%, 3.92%, 3.73%, 3.45% and 2.74%, however, there was no statistical difference in thrombosis rates between pts with or without the above gene mutations (EGFR, p = 0.90; c-Met, p = 0.23; ALK, p = 0.85; HER-2, p = 0.28; KRAS, p = 1.00; ROS1, p = 0.58). In the correlation analysis between the driving gene status and the thrombus status, the Spearman correlation coefficient was -0.024, and no statistically significant difference was observed (p = 0.69). Based on the Khorana model, the thrombosis rates of the low-, intermediate- and high-risk subgroups in the mutation group and non- mutation group were 0% vs 0%, 10.23 vs 8.33%, and 6.67% vs 12.50% respectively, which didn’t show statistically significant differences (low- risk, p = 1.00; intermediate-risk, p = 0.85; high-risk, p = 0.59). For the whole patient set, mutation group and non-mutation group, the Khorana model predicted venous thrombosis with the sensitivities of 13.33%, 10.00% and 20.00%, as well as the specificities of 92.02%, 92.55% and 90.67%; and the area under the ROC curve were 0.706 (p = 0.007), 0.719 (p = 0.02) and 0.681 (p = 0.18), respectively. Conclusions: The Khorana model has a moderate diagnostic value, and there is no correlation between the driving gene status of cancer pts and venous thrombosis.
Clinical insights for hematological malignancies from an artificial intelligence decision-support tool.
Authors: Kim Miyoung , Snowdon Jane , Weeraratne S Dilhan , Felix Winnie , Lim Lionel , Dankwa-Mullan Irene , Lee Young Kyung , Lee Eunyup , Jeon Kibum , Lee Jee-Soo , Zang Dae Young , Kim Hyo Jung , Kim Ho Young , Han Boram 
Published: May 2019

e13023 Background: Next generation sequencing (NGS) in hematological tumors is increasingly shaping clinical treatment decisions at the point of care. While the impact of NGS panels in solid tumors is largely therapeutic, targeted sequencing in hematological tumors can additionally provide diagnostic and prognostic insights. Additional data generated in hematological tumor sequencing makes manual interpretation and annotation of variants tedious and non-scalable. In this study we compared hematological tumor variant interpretation using an artificial intelligence decision-support system, Watsonä for Genomics (WfG), with expert guided manual curation. Methods: Patients with hematological tumors at Hallym University, College of Medicine between December 2017 and December 2018, were sequenced using the 54 gene Illumina TruSight Myeloid Panel. WfG interpreted and annotated all patients’ sequencing results, a subset of which were assessed manually to ascertain concordance. Results: 54 South Korean patients with hematological malignancies were analyzed (23 Acute Myeloid Leukemia, 12 myeloproliferative neoplasm, 5 myelodysplastic syndrome, 5 multiple myeloma and 9 others). Comparison of manual and WfG interpretation of 10 randomly selected cases yielded 90% (9/10) concordance and identification of 9 clinically actionable variants (33%) not found in manual interpretation. In total, WfG identified that 71% (38/54) of all cases had at least one clinically actionable therapeutic alteration (a variant targeted by a US FDA approved drug, off-label drug, or clinical trial). 33% (18/54) of cases had genes that were targeted by a US FDA approved therapy including JAK2, IDH1, IDH2, and FLT3. In cases without therapeutic alterations, WfG identified diagnostic or prognostic insights in an additional 20% (11/54) of patients. 9% (5/54) had no clinically actionable information. Conclusions: WfG variant interpretation correlated well with manually curated expert opinion and identified clinically actionable insights missed by manual interpretation. WfG has obviated the need for labor-intensive manual curation of clinical trials and therapy, enabling our center to exponentially scale our NGS operations.