bluuebunny/crossref_metadata_2025_split huggingface dataset:
A breakthrough in treatment of cancer patients with grade 4/profound febrile neutropenia.
Authors: Cainap Calin Ioan , Cainap Simona Sorana , Cetean- Gheorghe Sanziana , Leucuta Daniel Corneliu , Bochis Ovidiu Vasile , Gherman Alexandra 
Published: May 2019

e14513 Background: febrile neutropenia (FN) remains one of the most serious side effects of chemotherapy treatment, which is life-threatening. Late consequence of FN is dose reduction and delaying of therapies. Actual guidelines allows granulocyte-colony-stimulating factors (G-CSF) in management of profound FN in addition to antibiotics and supportive care Methods: it is an original prospective study, approved by local ethics comitee, which included 73 patients with confirmed malignancy, treated in our Institute with chemotherapy, who developed febrile neutropenia (FN) and were hospitalised. Patients with myeloablative chemotherapy and bone marrow transplantation support, severe renal impairment, abnormal liver function or with a history of allergic reactions to the antibiotics were excluded from the study. There were recorded 96 episodes of grade 4 FN (1-3 episodes / patients). Each of one was hospitalised according to institutional guideline but with a dose of G-CSF of 16 µg/Kg/day i.v. continous infusion Results: median age of included patients was 59 years, with approximately 48 % male and 52% female, whithout significance in terms of recovery from FN (p = 1.00). 30% of the patients had prophilactic G-CSF administrated, but not significant for recovery from aplasia for included patients (p = 0.34). Median chemotherapy line responsible for FN was 2, and median cycle which produced FN was 3. Median level of neutrophiles (PMN) 450/mm3 and leucocytes (WBC) 1875/ mm3 at time of FN, 10 patients being in profound FN (PMN < 100/mm3). Median time to recovery was 25.5 hours for 72 included patients, with 1 patient dead whithout recovery. Predictive factors for shortened recovery were lower levels of reactive protein C (p < 0.001) and procalcitonine (p = 0.002) and higher WBC (p = 0.006) and PMN (p < 0.001) at time of administration of responsible chemotherapy regimen for FN. The earlier cycle responsible, between a line of chemotherapy, for FN, the better chance for patient to have shortened duration of FN (p < 0.0001). Conclusions: continous i.v. administration of G-CSF could represents a very effective alternative for patients with profound febrile neutropenia, with the shortest ever reported interval for neutrophiles recovery
Pharmacokinetic/pharmacodynamic assessment of a proposed biosimilar MSB11455 versus the currently licensed pegfilgrastim: A randomized, double-blind trial.
Authors: Lickliter Jason D. , Griffin Paul , Vincent Emmanuelle , Schuler Armin , Harrison-Moench Eleanor , Stahl Michael , El Bawab Samer , Kanceva Radmila , Gascón Pere 
Published: May 2019

e14514 Background: MSB11455 is a proposed biosimilar to the currently licensed pegfilgrastim (Neulasta). This phase I study (NCT03251248) assessed the pharmacokinetic (PK)/pharmacodynamic (PD) bioequivalence of MSB11455 to Neulasta. Methods: Healthy volunteers were randomized to one of two crossover sequences, MSB11455/Neulasta or Neulasta/MSB11455. Subjects received a single subcutaneous dose of either MSB11455 or Neulasta (both 6 mg/0.6 mL) on Day 1 of each study period. Samples for PK/PD analysis were taken predose and up to Day 16 postdose. Immunogenicity samples were taken predose and up to Day 84 postdose. Safety was assessed throughout the study. Results: 244 subjects were randomized and received both treatments. For all primary PK/PD parameters 90% repeated confidence intervals of the geometric mean ratio of MSB11455 versus Neulasta were within the pre-defined equivalence range (80.00%–125.00%): AUC0–∞ (96.59, 112.82), AUC0–last (97.29, 113.96), Cmax (97.13, 114.99), Emax (98.74, 102.39) and AUE0–t (97.30, 100.23). Safety and tolerability as well as immunogenicity were comparable between treatment sequences. No filgrastim-specific neutralizing antibodies were detected in either treatment sequence. Conclusions: PK/PD equivalence of MSB11455 and pegfilgrastim was demonstrated with comparable immunogenicity, safety, and tolerability. This study supports the biosimilarity of MSB11455 to Neulasta. Clinical trial information: NCT03251248.
A highly efficient, low-cost, novel multicomponent nanosystem for rapid enumeration of circulating tumor cells.
Authors: Khandare Jayant , Qayyumi Burhanuddin , Prabhash Kumar , Chavan Rohit , Gourishankar Aland , Khatun Zamila , Mair Manish , Singh Arjun , Vasudevan Aravindan , Sagare Ajit , Chidara Vamshi , Bharde Atul , Chaturvedi Pankaj 
Published: May 2019

e14516 Background: ‘Liquid biopsy’ technologies are unaffordable and unavailable in developing countries despite having highest cancer burden and mortality rates. Current Circulating Tumor Cell (CTCs) technologies sustain clinical concerns of a) non-specificity b) low efficiency c) high blood volume requirement d) long turn-around time, and d) exorbitant cost (~$900-1400). We report, an extremely low cost, innovative nanosystem for rapid enumeration of CTS with higher specificity and efficiency. Methods: We designed a nanosystem mediated by conjugation of anti-EpCAM through multi-reactive glutathione spacer, carbon allotrope and amine terminated dendrimer. The platform was evaluated for enhanced aqueous dispersibility and increased interaction with CTCs for rapid isolation and enumeration in 100 Head and Neck Cancer (HNC) patients having primary tumor sub-sites-oral cavity, larynx, hypopharynx, oropharynx, nasopharynx, salivary gland, and thyroid. The captured cells were immuno-stained and the optimal fluorescence acquisition intensity was validated in accounting CTCs with CK18 protein expression. There was complete elimination of the false positive normal cells (NC) count to CTCs by our method. The analysis was performed with only 1.5 ml of collected blood samples. Results: The CTC distribution in cohort study ranged from 1 - 85 cells per 1.5 mL of blood. In more than 80% of patient’s CTCs, the quantitative estimation of anti-CK18 protein over-expression indicated ~10-fold higher intensity over to NCs. As compared to treatment naive, recurrent, and disease-free patients, the spread of CTC number across the clinical range appeared to be tight (close to mean value). The CTC enumeration sensitivity linearity was ~99.2%, and the complete enumeration process time was under 03 hours/1.5 ml of blood. Consequently, efficient, rapid and yet affordable CTC platform was designed and clinically validated. Conclusions: ‘OncoDiscover’ liquid biopsy technology for CTC enumeration is poised to revolutionize the liquid biopsy due to its high sensitivity and affordability (~ $120) and shall resolve a major unmet medical need in impoverished world.
Systemic immune-inflammation index to predict prognosis of elderly patients with newly diagnosed solid tumors.
Authors: Li Chan , Tian Wei , Zhao Feng , Li Meng , Ye Qin , Wei Yuquan , Li Tao , Xie Ke 
Published: May 2019

e14517 Background: Cancer in the elderly has become a common problem due in part to the increase in life expectancy. Compared to younger counterparts, the biological characteristics of tumors and their responsiveness to therapy may differ in elderly patients, and the elderly also can have a decreased tolerance to anticancer therapy. In addition, there is less evidence from clinical trials to guide physicians in treating aged patients with solid tumors. It would be highly useful to have a simple and powerful indicator of their prognosis. In this paper we evaluated the predictive value of the Systemic Immune-inflammation Index, SII, in determining the one-year survival in elderly patients with newly diagnosed solid tumors. Methods: Data from 118 patients, 70 to 89 years of age with newly diagnosed solid tumors in 2014 were retrospectively analyzed. The patients were divided into two groups according to age: (1) 70-75 years of age and (2) over 75 years of age. We calculated SII from the equation, SII = P x N/L, where P, N and L are the preoperative peripheral blood platelet, neutrophil and lymphocyte counts per liter respectively. The optimum cutoff point for SII for a favorable prognosis was determined to be 390×109 cells/L. For evaluation of SII as a prognostic indicator, the patients were divided into high SII ( > 390×109 cells /L) and low SII (≤ 390×109 cells/L) groups. Individual values were used to determine the relationship between SII and one-year survival in the two age groups. Results: A high SII > 390×109 cells/L was correlated with poor one-year survival (χ² = 7.658, P = 0.006). Patients with low SII had improved survival. Conclusions: SII was a robust indicator of one-year survival in elderly patients with newly diagnosed solid tumors. Patients in the high SII group showed poor prognosis compared to patients with a low SII score. [Table: see text]
EGF (epidermal growth factor) receptor expression in blood: Prognostic biomarker in overall survival (OS) of patients with non-metastatic triple negative (TN) breast carcinoma.
Authors: De Araujo Rogerio Agenor , da Luz Felipe Andrés Cordero , do Amaral Pedro Augusto , Marinho Eduarda da Costa , Nascimento Camila Piqui , Mosca Etelvina Rocha , Delfino Patricia Ferreira Ribeiro , Antonioli Rafael Mathias , Mendes Thais Rezende , Araújo Breno Jeha , Silva Marcelo José Barbosa , Neto Morun Bernardino 
Published: May 2019

e14518 Background: EGF acts on tumor progression and its receptor can be measured by immunohistochemistry, or in the blood by immunoenzymatic method. This study quantified the expression of blood EGF receptors (bEGFR) in the molecular subtypes of breast carcinoma and their impact on OS. Methods: Prospective study with 125 patients (pts) and 89 healthy women (controls). All of them signed the free and detailed consent form. The blood collection was performed before the surgery (stages I–10pts; II–59pts) and before neoadjuvant chemotherapy (stage III-41pts) or palliative (stage IV–15pts). All the patients have made the protocol of a public service treatment. Measurement of bEGFR expression was done by the ELISA method. The statistical significance was set at p < 0.05. Results: In a follow-up of 29.9 months (8-44m) 23 deaths occurred at 15.8 months (8-34.5m); 58pt had bEGFR < 40ng/mL (E40-) and 67pt ≥40ng/mL (E40 +). TNs (28pt) had lower OS than Luminal (A = 29pts; B = 44pts) and HER2 (24pts) (p = 0.0020). But in TN E40- the significant difference in OS disappeared (TN versus Luminal A: p = 0.0785; TN versus Luminal B: p = 0.1995; TN versus HER2: p = 0.3017); which did not occur in TN E40 + (TN versus Luminal A: p = 0.0009; TN versus Luminal B: p = 0.0241; TN versus HER2: p = 0.0014). In OS of non-metastatic 24 TN (3pts stages 0/I; 13pts II; 8pts III) there was significant difference according to bEGFR expression (E40+ with lower OS than E40-, HR:5.49; 95%CI:1.26–15.07;p = 0.0159). In binary logistic regression, bEGFR was considered to be a significant predictor of death in TN non-metastatic, p = 0.008 (bEGFR of 30ng/mL = death probability of 6.7% until bEGFR of 80ng/mL = probability of death of 99.8%). There were no significant differences in bEGFR between patients and controls, among grades of histological differentiation, or in those with ki67 > 14%. There was no difference in OS according to bEGFR in stages I, III or IV, except in stage II (E40+ with lower OS than E40-, HR:4.248;95% CI:1.229–14.68; p = 0.0460). Conclusions: Increased expression of bEGFR in non-metastatic TNs is a predictor of lower OS, with statistical significance.
Association of forkhead box protein O1 and paired box gene 3 overexpression with prognosis in patients with cervical cancer.
Authors: Cho Hanbyoul , Han Gwan Hee , Chay Doo Byung , Kim Jaehoon 
Published: May 2019

e14519 Background: Transcriptional factor FOXO1and PAX3 has been reported to play an imported role in human cancer, but the role in cervical cancer has not yet been clarified. Here, we evaluated the functional role of FOXO1 with cervical cancer cells and the expression together with clinical significance of FOXO1 and PAX3 among cervical lesions was investigated. Methods: In vitro assessment of cell functions by cell viably assay, cell migration and invasion assay was evaluated using FOXO1 knockdown cervical cancer cell lines. Immuno-histochemical (IHC) staining analyses of FOXO1 and PAX3 were performed with tissue microarray (TMA) consisting of 209 cervical cancers, 366 high grade cervical intraepithelial neoplasias (CIN), 130 low grade CIN and 328 matched nonadjacent normal cervical epithelial tissues. The clinical significance was investigated by comparing the data with various clinicopathologic characteristics, including survival in cervical cancer. Results: In vitro result revealed that knockdown of FOXO1 was associated decreased cell viability ( p< 0.001), migration ( p< 0.001) and invasion ( p< 0.05) supporting the oncogenic role of FOXO1 in cervical cancer. FOXO1 and PAX3 expression was significantly higher in CIN (both p< 0.001) and cancer tissue (both p< 0.001) than in normal tissue. FOXO1 expression showed significant correlation with PAX3 (Spearman’s rho = 0.377, p< 0.001) in a cervical cancer. Multivariate analysis indicates that FOXO1 expression (hazard ratio = 4.01 [95% CI, 1.22–13.10], p= 0.021) and advanced FIGO stage (hazard ratio = 3.89 [95% CI, 1.35–11.19], p= 0.012) were independent prognostic factor on overall survival. Conclusions: This study reveals the association between FOXO1 and PAX3 expression with clinicopathologic variables, including survival of cervical cancer patients. Our results not only suggest the promising potential of FOXO1 as a prognostic and survival marker, but also warrant further studies on a possible link between the biological function of FOXO1 and the pathogenesis of cervical cancer.
Detection of low abundant mutants from circulating tumor DNA of plasma, pleural effusion, and cerebrospinal fluid of lung cancer patients using a novel mutant-capture enrichment approach.
Authors: Lin Rui , Pu Yue , Mao Li 
Published: May 2019

e14520 Background: In the era of precision medicine, liquid biopsy analysis is well accepted based on advantages including availability, non-invasiveness, and non-heterogeneity. However, the circulating tumor DNA (ctDNA) in liquid biopsy is diluted by a large excess of wild-type alleles, which necessitates high sensitivity approach for ctDNA detection. In addition, ctDNA analysis from different liquid biopsy samples need to be evaluated. Methods: We have developed a novel mutant-capture based method, termed PErsonalized Analysis of Cancer (PEAC), for high sensitivity detection of cancer driver mutants at abundance as low as 0.01-0.1% for circulating free DNA (cfDNA) standards. ctDNA samples were extracted from body fluids of lung cancer patients including plasma, pleural effusion and cerebrospinal fluid. EGFR mutants predictive of EGFR tyrosine kinase activity were enriched using PEAC technology, and analyzed using Sanger sequencing. Results: Plasma ctDNA samples B7110003, B7110010, and B7112012 had no or barely detectable L858R mutation, which was enriched to 50-90% after PEAC and readily detected by Sanger. T790M was undetectable before PEAC in plasma sample B7112052 and became 50% after PEAC enrichment. Pleural effusion samples E8106029 and E8111305 had dominated L858R and T790M peaks, respectively, in Sanger chromatograms after PEAC, which was almost to the background levels prior to PEAC. Interestingly, both EGFR L858R and T790M mutants were detected in pleural effusion sample E8106029 after PEAC; the sample was from a patient who had previously treated with an EGFR tyrosine kinase inhibitor (TKI), suggestive of resistance developed after target therapy and the utility of PEAC in monitoring patient’s response to EGFR TKI. In addition to enriching point mutations, we also established enrichment of the most frequently occurred EGFR 19 deletion, E746_A750del (c. 2235_2249 del15), which were dominant after PEAC enrichment of ctDNA from plasma samples (B8101186 and B8101241), pleural effusion (E8108088) and cerebrospinal fluid (C8108095); the mutants were undetectable without PEAC enrichment. Conclusions: PEAC technology can enrich ctDNA from body fluids in lung cancer patients and allow detection of low abundant mutants predictive for EGFR TKI therapy. With further validation, the technology may improve current detection methods used in clinical practice.
Elevated plasma cell-free DNA copy number variations to predict survival for cancer patient with spinal metastasis.
Authors: Chen Su , Yang Minglei , Zhong Nanzhe , Ziliang Qian , Jiao Jian , Xiao Yasong , Jiang Dongjie , Zhou Zhenhua , Wang Tianzhen , Lou Yan , Xu Wei , Wan Wei , Wu Zhipeng , Yang Cheng , Wei Wei , Liu Tielong , Zhao Jian , Wei Haifeng , Yang Xinghai , Xiao Jianru 
Published: May 2019

e14522 Background: Approximately 70% of patients with cancer have evidence of spinal metastatic disease at the time of their deaths. The spinal column is the most common location among osseous sites for metastatic deposits. Expected overall survival is the major determinant of treatments for those ones suffering from intractable pain, neurologic deficits, and even paralysis. We sought to evaluate copy number variations (CNV) in spinal metastatic cancer via cfDNA and determine if CNV is associated with prognosis and treatment decision. Methods: In this study, 314 patients with pathologically confirmed spinal metastatic cancers were recruited since November 2015. 314 plasma samples were sent to low-coverage genome-wide sequencing of cfDNA from plasma followed by a customized bioinformatics workflow UCAD. Tokuhashi score was also evaluated for each patient before surgery. Statistical correlation with clinical index like prognosis was estimated. Results: 280 evaluable data were collected (34 samples failed Quality Control). The median follow-up time is 276 days. 114 (40.7%) patients died during follow up till December the 25th, 2018. Elevated CNVs was found in 109 (38.9%) patients, including 9(69.2%) head&neck, 15(46.9%) liver and gallbladder, 27(44.3%) lung, 7(38.9%) breast, 2(28.6%) prostate, 5(19.2%) thyroid cancer, 4 (10.5%) kidney and 20(40.0%) cancer with unknown primary site. Further analyses showed that patients with elevated CNVs were found with worse survival. The median overall survival (OS) was 298 (95% CI: 258-422) days, as compared with those low-CNVs status with median OS 657 (95% CI:433-NA) days (Hazard ratio = 3.73 [95% CI: 2.22-6.27], P < 0.01). Especially for patients with low Tokuhashi score (≤8) who have the predictive survival less than 6 months, CNVs score distinguish those well-prognosis patients with median OS 433 (95% CI: 308-NA) days from the worse survival group with median OS 285(95% CI:243-348) days (Hazard ratio = 2.42 [95% CI:1.38-4.25], P = 0.013). Conclusions: We present the largest cfDNA genomic characterization of spinal metastatic cancers. Specific CNVs features are enriched in spinal metastasis cancers with different primary sites. Elevated CNVs in plasma cfDNA is significantly associated with worse survival in a large spinal metastatic cancer cohort. This demonstrates that cfDNA CNVs could be a useful marker in estimating the survival time of spinal metastasis cancer patients for whom the outcome is mainly dependent on the selection of proper treatment.
Epigenomic profiling of plasma cell-free DNA (cfDNA) to predict bladder cancer recurrence after radical cystectomy.
Authors: Lu Yi-Tsung , Gooden Gerald C , Tew Ben Yi , Buckley David , Siegmund Kimberly , Daneshmand Siamak , Salhia Bodour , Goldkorn Amir 
Published: May 2019

e14525 Background: Muscle invasive bladder cancer (MIBC) frequently recurs despite radical cystectomy, and new biomarkers are needed to guide treatment. DNA methylation plays a key regulatory role in cancer initiation and progression and has been correlated with prognosis in multiple cancer types. We hypothesized that methylation patterns in cfDNA can predict recurrence after curative cystectomy. Methods: Using a clinically annotated USC bladder cancer tissue archive under an IRB approved protocol, we selected 40 patients whose cancer relapsed within 3 years of radical cystectomy, as well as 46 age-matched and stage-matched patients who did not recur after 3 years of follow-up. cfDNA was extracted from the archival plasma, and samples were pooled for whole genome bisulfite sequencing (WGBS) based on pathologic stage and recurrence status. Differentially methylated regions (DMRs) was identified between recurrence and non-recurrence groups in each stage. Results: Pooled analysis across stages yielded 729 DMRs, of which 487 (67%) were hypomethylated in the pooled recurrence group. Of the 729 DMRs from the pooled analysis, 63.5% were in gene bodies, 17.1% were in promoter regions and 47.9% were at CPG islands. Unsupervised clustering of these DMRs accurately distinguished the recurrence groups. Stage-specific analysis yielded DMR sets ranging from 6412 to 9532 DMRs per stage, with a similar trend of global hypomethylation in the recurrence groups. Basespace Correlation Engine analysis revealed that methylation in our recurrence groups (pooled and by stage) was correlated with bladder cancer methylation in publicly available data and also correlated with expression in the TCGA bladder cancer dataset. Conclusions: WGBS was successfully performed in MIBC using cfDNA extracted from clinically annotated archival plasma. Methylation patterns were correlated with publicly available methylation and expression datasets, and cfDNA hypomethylation pre-cystectomy in our cohort was associated with cancer recurrence. A subset of maximally discriminatory DMRs has been selected to define a methylation signature that is currently undergoing validation as a biomarker predictive of recurrence in MIBC.