bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single-center study of cancer and chemotherapy-induced kidney disease.
Authors: Mirza Abu-Sayeef , Mushtaq Sarah , Reddy Revati , Mousa Mina , Bohra Chandrashekar , Kongpakpaisarn Kullatham , Verma Sean , Mhaskar Rahul Suresh , Jaglal Michael Vishal , Bassil Claude 
Published: September 2018

e13062 Background: It is clinically understood that chronic kidney disease (CKD) and cancer are interrelated. Yet, few studies measure how renal outcomes vary according to common malignancies and common therapeutic agents. We report the incidence and the nature of CKD among cancer patients from a single institution. Methods: A retrospective chart review of cancer patients managed in the onconephrology clinic at the Moffitt Cancer Center from 05/01/2015 to 07/31/2016 was conducted. Patients with acute or chronic kidney disease secondary to a malignancy or side effect of chemotherapy were included in this study. Renal function outcomes were recorded at three-month follow-up intervals from the 15-month duration. Results: Out of the total 88 patients with median age of 68 years, 63 patients were diagnosed with chronic kidney disease, whereas the remaining had acute kidney injury. Kidney cancer and multiple myeloma represented the largest proportion with 12 patients each. Patients with kidney cancer had a mean creatinine of (2.35, 1.74) mg/dl compared to patients without kidney cancer with creatinine (1.97, 1.07) mg/dl. Abdominal cancers had the highest proportion of chronic kidney disease (84.21%) whereas 81.48% of patients with genitourinary cancers had chronic kidney disease. Patients prescribed tyrosine kinase inhibitors had a lower average estimated glomerular filtration rate (28.37, 9.86) mL/min/1.73 m2 compared to other chemotherapeutic agents, though this was a weakly significant relationship (p-value = 0.07). Similar renal outcomes according to malignancy and chemotherapy are reported. Conclusions: This group of patients demonstrated the frequency of chronic kidney disease differs depending on the type of malignancy or chemotherapy. A multidisciplinary approach involving oncologists and nephrologists should be adopted to prevent further renal damage from cancer and its therapies.
Striking age differences of multiple myeloma (MM) diagnosis in patients of Indian and Pakistani descent in the United States compared to native countries.
Authors: Unnikrishnan Athira , Khan Abdullah Mohammad , Narayan Preeti , Norkin Maxim 
Published: September 2018

e13070 Background: Several studies from India and Pakistan have reported a median younger age of MM diagnosis as compared that of western population. The exact reason for the younger age of myeloma diagnosis in this population is not well understood. Methods: We used the SEER database to analyze age of MM diagnosis in subjects of Indian and Pakistani descent in the United States and compared it to the published data of MM diagnosis in India and Pakistan. Patients with ICD—O-3 morphologic codes (9732/3) and race code 15/16/17 identifying Asian Indians and Pakistanis were identified in the SEER registry data (1973-2013). Data on year of diagnosis, race, sex and age were collected. Four published retrospective studies involving local Indians or Pakistanis patients identified using PUBMED. Average Median age and male to female ratio (M: F) was calculated in both groups and compared for any difference Results: 146 myeloma patients of either Indian or Pakistani descent were identified from the SEER registry. The median age of diagnosis was 67 years with a mean age of 66.1 years. The male to female ratio was 1.41. The retrospective studies analyzed had a total of 495 myeloma patients with median age at diagnosis of 56 years and male to female ratio of 2.01, suggesting that multiple myeloma presented almost a decade earlier in native Indian and Pakistani patients compared to their US counter parts. Conclusions: Subjects in India and Pakistan were significantly younger at the time of MM diagnosis as compared to subjects of Indian and Pakistani descent diagnosed with MM in the US suggesting an environmental factor involved with myeloma genesis in subjects living in India and Pakistan. [Table: see text]
Preliminary analysis and assessment of breast cancer risk in Japanese women.
Authors: Yamada Michiyo , Ishikawa Takashi , Sugae Sadatoshi , Narui Kazutaka , Arita Eiji , Tonellato Peter , Endo Itaru , Chishima Takashi 
Published: September 2018

e13092 Background: No comprehensive breast cancer risk assessment model for Japanese women exists. Consequently, we have collected Japanese women’s data to investigate key BC risk factors with an objective of deriving a Japanese-women specific BC risk assessment model. Methods: We conducted a retrospective case-control study (paper-based with postal survey) at 15 institutions during 2014-2015. A survey was distributed to Japanese females aged 20-80 who had BC check-up. All pertinent data of a total of 34 factors including demographic and reproductive factors, social history and eating habits was collected. Cases and controls were divided into three groups respectively, premenopausal (PRE; 20 ≤ age < 45), perimenopausal (PERI; 45 ≤ age ≤ 55) and postmenopausal group (POST; 55 < age ≤ 80). Cases and control variables were compared by t-test, chi-square test and Wilcoxon rank sum test. Preliminary BC risk was calculated by logistic regression analysis. Results: A total of 3975 female Japanese datasets were collected, of which 2494 were complete (all variables present) with 1401 controls and 1093 cases were used. There were 222 cases and 332 controls for PRE, 404 cases and 537 controls for PERI, and 467 and 532 controls for POST. The univariate analysis demonstrated that BMI was significantly higher in cases than in controls in all groups (P < 0.01) as was “number of deliveries” in PRE and POST (P < 0.001) and Brinkman index in PRE and PERI (p = 0.017). Multivariate analysis revealed that BC risk was positively associated with BMI (OR 1.080, 95% CI 1.017–1.148, p = 0.012) in PRE, BMI (OR 1.121, 95% CI 1.072–1.174, p < 0.01) and brinkman index (OR 1.000005, 95% CI 1.000002–1.000008, p < 0.01) in PERI, age (OR 1.054, 95% CI 1.028–1.081, p < 0.010), BMI (OR 1.153, 95% CI 1.076-1.171, p < 0.01) and family history (OR 1.497, 95% CI 1.103–2.033, p = 0.001) in POST, while negatively associated with regular exercise (OR 0.672, 95% CI 0.517–0.873, p = 0.003) in POST. Conclusions: BMI in all groups, in addition, the Brinkman index in PERI and age and family history in POST are BC risk factors. Exercise is a protective risk factor in POST. However, the preliminary results are incomplete and further analysis will be conducted before a full risk assessment model is proposed for Japanese women.
Effects of county-level attributes on geographic variation in female breast cancer mortality rates across counties in United States.
Authors: Sagiraju Hari Krishna Raju , Jatoi Ismail , Valerio Melissa , Chien Lung-Chang , Gimeno David 
Published: September 2018

e13093 Background: Though studies have examined geographic disparities in breast cancer mortality among United States (U.S.) counties, county-level risk factors were not accounted for. The aim of this study is to efficiently map the spatial association between female breast cancer mortality rates & socioeconomic attributes across U.S. counties for identifying high risk geographical clusters in terms of socioeconomic attributes. Methods: County-specific age standardized breast cancer mortality rates for women ≥20 years in the U.S. were obtained for 3,109 counties in 48 contiguous states from Surveillance Epidemiology and End Results program from 1990-2012. County-level attributes such as percentages of Hispanic white, Non-Hispanic white, Non-Hispanic black, < high school education, below 200% poverty, urban, foreign born, language isolation, women aged ≥ 40 years with mammography within last 2 years, and median household income were gathered from U.S. decennial census. Factor analysis condensed county attributes into three factor covariates namely Hispanic immigrants, health care access among urban high socioeconomic population, and non-Hispanic black unemployment. Spatiotemporal analysis was carried out by structured additive regression model to incorporate spatial functions & Markov chain Monte Carlo simulation techniques. Results: Moran’s index suggested existence of spatial dependence for breast cancer mortality among U.S. counties. As mammography screening, %urban population, % with high socioeconomic status and non-Hispanic black unemployment increased in counties of the Southwest region, Rocky mountain region and those in the western border of Midwest region of U.S, risk of breast cancer mortality increased significantly above the national average. As the Hispanic immigrant culture increased, counties of Midwest region of U.S had significantly higher mortality rates compared to national average. Conclusions: These initial results describe socio-economic, cultural, and healthcare access factors for observed geographic variations in female breast cancer mortality, and in turn, could support a stronger theoretical basis for public health policy.
Multiplex ALK, RET, and ROS1 fusion mutation detection in FFPE from lung cancer patients by MALDI-TOF mass spectrometry.
Authors: Su Kang-Yi , Ho Bing-Ching , Chang Gee-Chen , Chen Hsuan-Yu , Yang Pan-Chyr , Yu Sung-Liang 
Published: September 2018

e13103 Background: Approximately 3-7% of lung tumors harbor anaplastic lymphoma kinase (ALK) fusions in the subgroup of non-small cell lung cancer (NSCLC). In addition to echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion, TRK-fused gene (TFG)-ALK, kinesin family member 5B (KIF5B)-ALK and kinesin light chain 1 (KLC1)-ALK had been reported in lung cancer. On the other hand, RET proto-oncogene (RET) and ROS proto-oncogene 1 (ROS1) fusion proteins also have prevalence in lung cancer. Food and Drug Administration (FDA)-approved several target drugs are available to treat patients with fusion mutations. Therefore, the diagnosis of ALK, RET or ROS1 fusion genes shows quite important. However, nowadays methods of detecting fusions such as fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are limited to technique, low sensitivity, sample quality as well as subtype classification. Methods: We established nucleotide MALDI-TOF mass spectrometry based multiplex detection platform to distinguish major types including 9 types of EML4-ALK, 5 types of ALK, 5 types of RET and 8 types ROS1 fusions. Results: The detection limitation was about less 1% mutant cells among wild-type cells. In the pilot testing, we used 2 patients’ cell cDNA and 4 patients’ lung FFPE samples cDNA, which had been diagnosed as ALK fusion before, to be detected by this panel, and then identified their variant types successfully. Furthermore, one patient harbored CCDC6-RET fusion mutation was identified by our platform and confirmed by Sanger Sequencing. Conclusions: Taken together, this new panel has high sensitivity and allows little and poor quality samples for detecting. The correlation between clinical characteristics and fusion subtypes can be further investigated by utilizing this platform in the future. Also, the detection panel can be revised based on clinical needs by removing/adding probes.
BRCA 1/2 mutations by next-generation sequencing testing in 200 Romanian high-risk patients with breast cancer.
Authors: Eniu Alexandru E. , Antone Nicoleta Zenovia , Stoian Andrei , Dronca Eleonora , Matei Ramona DOINA , Ligtenberg Marjolijn , Ouchene Hicham , Eniu Rares , Pop Laura 
Published: September 2018

e13116 Background: To determine types and frequencies of BRCA 1 (B1) or BRCA2 (B2) mutations in high-risk Romanian breast cancer patients, as there is no data published in this population. Methods: This prospective study evaluates the germline BRCA1/BRCA2 mutations in 200 Romanian high-risk breast cancer patients tested between February 2015-January 2017 at IOCN. Inclusion criteria selected patients diagnosed with breast cancer before 40 years, triple negative breast cancer under the age of 50, or having conventional family history criteria. All patients signed an informed consent. BRCA1/BRCA2 testing was performed using an AmpliSeq-based sequencing analysis, on the Ion Torrent Personal Genome Machine (Life Technologies) at RCFG. The pathogenic mutations were validated using Sanger technology. MLPA was performed for all 200 patients. Results: We analyzed 200 high-risk breast cancer patients and found 32 (16%) patients with pathogenic mutations, 23 (11.5%) patients with B1 and 9 (4.5%) patients with B2 mutations. The majority of patients (99.5%) presented normal MLPA results; only one sample (0.5%) presented a deletion at CHEK2-9(10). The frequency of class 5 mutations identified in B1 gene were c.1687C > T (1%), c.181T > G (2%), c.3607C > T (3.5%), c.4218delG (0.5%), c.5329_5330insC (c.5266dupC) (4.5%) and for the B2 gene c.1528G > T (0.5%), c.4022C > G (0.5%), c.7007G > A (0.5%), c.8695C > T (0.5%), c.9253 delA (0.5%), c.9371A > T (2%). Conclusions: Frequency of deleterious BRCA mutations in our cohort was 11.5% for BRCA1 and 4.5% for BRCA2. This prospective study presents the first extensive results on frequency and types of germline BRCA1/2 mutations in Romanian high-risk breast cancer patients. Clinical trial information: NCT02317120. [Table: see text]
Mutational profiling of Chinese ROS1 positive non-small cell lung cancer patients with required resistant to crizotinib by next generation sequencing.
Authors: Wang Wen-xian , Xu Chunwei , Fang Meiyu , Zhu You-cai , Chen Yan-ping , Chen Yu , Liao Xing-hui , Zhuang Wu , Lin Gen , Chen Xiao-hui , Huang Yun-jian , Xu Hai-peng , Du Kai-qi , Guan Yan-Fang , Yi Xin , Chen Gang , Lv Tangfeng , Song Yong 
Published: September 2018

e13120 Background: The ROS1 rearrangement has been identified in 1%-2% of NSCLC cases, these patients would benefit from the inhibitor of crizotinib. But the resistance to crizotinib inevitably developed in the patients with ROS1+ NSCLC and shown a response to crizotinib initially. The mechanism of acquired resistance to crizotinib for the patients with ROS1+ NSCLC is not identified completely now. In this study, we performed mutational profiling in a cohort of 16 ROS1+NSCLC patients at diagnosis and acquired resistance to crizotinib using targeted NGS. Methods: A total of 16 patients with stage IIIb-IV ROS1+ NSCLC were undergoing tumor biopsies or blood withdrawing by the time of acquiring resistance to crizotinib, including 4 formalin-fixed paraffin-embedded (FFPE) samples, 9 serum samples and 3 serous effusions. We used targeted NGS to detect genes status of patients. Results: In total, we identified 62 genetic alterations with a median of 3.9 mutations per patient. 93% of patients still exhibit fusions, and 31% of patients acquired ROS1 required point mutations. Besides other known resistance mechanisms, we identified CDKN2A mutations in 19% of patients. Interestingly, we also observed TERT, PTPRD, NFE2L2 and OR5L2 mutations in ROS1 required point mutations negative patients, which were restricted to crizotinib resistance. Conclusions: Our study uncovered mutational profiles of ROS1+NSCLC patients with crizotinib resistance with potential therapeutic implications, and this study also depicted the genetic landscapes comprehensively in Chinese ROS1+NSCLC population resistant to crizotinib. Our analysis demonstrates new perspectives for further study of resistance and putting forward corresponding relevant tactics against the challenge of disease progression.
Pattern of blood count change during craniospinal irradiation and the effect on progression free survival in medulloblastoma adult patients.
Authors: Dibs Khaled Nabil , Jaradat Imad A. , Khader Jamal , Al Khairi Laith , Sarhan Nasim , Mohammad Ahmad , Sulaiman Awf , Amoudi Mohammad , Ismael Yousef , Hijlih Ramiz , Ghatasheh Hamza , Al-Mousa Abdelatif 
Published: September 2018

e13500 Background: The primary treatment of medulloblastoma in adults is surgery followed by radiotherapy. Craniospinal irradiation in such patients holds a clinical significant effect on blood count drop, as more than 50% of bone marrow is irradiated during CSI. Precise guidelines on how often a patient's peripheral blood count should be monitored are yet to be established. Methods: A retrospective analysis of blood count data on 42 adult medulloblastoma patients who underwent surgical resection followed by CSI as 36-39.6Gy over 20-22 fractions followed by boost to posterior cranial fossa up to 54Gy and spinal boost up to 45Gy. The manner of blood count cells during radiotherapy and the correlation between WBC drop and outcome were examined. Results: Our study showed a drop in WBCs to 4 and below in 64% of patients during CSI. Eight patients (19%) had Hb drop below 12. There was no grade 3 or 4 anemia. Significant drop in neutrophils below 1500 was observed in 8 patients (20%), with 2.4% had grade 3 neutropenia. In 26 patients (62%) who developed platelets drop, three patients (7%) had platelets of less than 50000 (grade 3 and 4 thrombocytopenia). The Hb, lymphocyte, neutrophils, and platelets nadirs were 8.7 g/dL, 42 cells /microL, 720 cells /microL, and 1000 platelets/microL, respectively. The minimum interval between the nadir and starting radiotherapy for Hb, WBCs, and platelets were 13, 6, and 11 days, respectively. The median interval between the nadir and starting radiotherapy for all cells was 3 weeks. The median WBCs percentage drop was 71%. In 23 patients who had non-metastatic disease, the estimated three year progression free survival was 70%. In those who had WBC drop below 2.7 the PFS was 100% vs. 46%. (P value = 0.042). Conclusions: Some institutions reduced monitoring of CBC during conventional radiotherapy may result in financial saving; however, our study suggests the need for weekly CBC for patients receiving CSI irradiation. Fortunately, no one developed serious infection during radiotherapy, but a precaution should be there. A WBCs change during radiotherapy could reflect the outcome and may suggest more aggressive treatment in patients who had a nadir of 2.7 and above.
Expression of metabolic enzymes as predictors of prognosis in patients with aggressive primary brain cancers.
Authors: Schwartz Kenneth A. , Noel Mary , Shaik Mohammed , Chang Howard , Olson L. Karl 
Published: September 2018

e13529 Background: Aggressive primary brain cancers like glioblastoma multiforme (GBM) are metabolically active tumors. We hypothesis that abnormalexpression of metabolic enzymes may be useful in predicting survival. Methods: 60 patients (45 with GBM, 11 with anaplastic gliomas and 4 with gliosarcoma) were evaluated using Immunohistochemistry (IHC) to measure the relative expression of metabolic enzymes known to be predictors of prognosis including hexokinase-II (HK2) and mutated isocitrate dehydrogenase-1 (IDH1-R132H) as well as several ketolytic enzymes including cytosolic type 2 (R)-beta-hydroxybutyrate dehydrogenase (BDH2)..The tumors were graded based on the percentage of immunoreactive tumor cells: Positive (≥20%), Negative ( < 20%). Survival was calculated using Kaplan Meier (KM), and an age adjusted hazard ratio (aHR) for death was obtained using cox proportional analysis for enzyme expression. Significance p ≤0.05. Results: Demographics for 60 patients; 19 females and 41 males, median age 62 years, and median survival for all the patients 5.9 months. Univariate analysis showed positive HK2 and negative BDH2 expression had decreased survival with (HR of 1.8 p = 0.06 and 2.6 p = 0.01), respectively. In a multivariate analysis after adjusting to age, histology and other enzyme expression, positive HK2 and negative BDH2 expression were statistically associated with decreased survival (aHR of 11.3 p = 0.001 and 32.6, p = 0.0004), respectively. The group with favorable prognosis (negative HK2 and positive BDH2 expression) (n = 36) had a median survival of 9.7 months (95% CI 4.2 -13.5) whereas the group with non-favorable prognosis (neither a negative HK2 nor a positive BDH, n = 24) had a median survival of 3.1 months (95% CI 1.8 – 5.8). Because only 3 patients had GBM that were positive for the IDH1-R132H mutant protein, IDH1-R132H was not used as a statistically valid predictor in this study. Conclusions: Our current result confirms the poor prognosis associated with positive expression of HK2, and suggests that negative IHC expression of BDH2 may be a new indicator of poor prognosis for patients with aggressive primary brain cancers.
Comparison of early versus late onset of cellular immunotherapy in glioblastoma multiforme WHO IV.
Authors: Nesselhut Jan , Marx Dagmar , Cillien Nicole , Chang Raymond Y. , Brockmann Wulf-Peter , Martin Michael , Nesselhut Thomas 
Published: September 2018

e13531 Background: Glioblastoma multiforme (GBM WHO grade IV glioma) is an aggressive disease with an unfavorable prognosis. The current first line treatment comprises radical operation and radiotherapy combined with temozolomide chemotherapy (Stupp protocol). After failure of first-line therapy there is currently no effective therapy. Here we report that dendritic cell therapy prolongs the survival for patients with newly diagnosed GBM V. Preliminary results show that adding checkpoint blockade with Nivolumab may cause a secondary therapy response. Methods: After isolating monocytes from peripheral blood of n = 11 patients with stage IV GBM, who underwent primary surgery and first-line radio-chemotherapy and from n = 34 patients, who failed first line therapy MoDC were generated using standard protocols. In 5 patients checkpoint blockade with Nivolumab was added after failure of DC therapy. Results: With a median overall survival of 41 months there is a clear improvement of the overall survival in patients, who received DC therapy after having finished the Stupp-protocol. The 3- year-survival rate after primary diagnosis is 46% (n = 5) and 1 patient is still alive after 81 months. In this patient a secondary therapy response of 16 months could be induced by adding low dose Nivolumab (1mg/kg body weight) after failure of DC therapy. The median survival after onset of DC therapy in patients who failed first line standard therapy is 10 months. The 3-year overall survival rate is 9% (n = 3). In 4 patients therapy with Nivolumab was combined causing only a limiting effect on the survival (4 to 10 months). Conclusions: Dendritic-cell based immune therapy started immediately after primary standard therapy has a clear impact on the overall survival of patients with newly diagnosed GBM IV. Whereas the therapeutic effect for patients after failure of first-line therapy is limited. Nivolumab may cause secondary therapy response in certain patients.