bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2605: Improving data quality in oncology immunotherapy clinical research by big data analytics and data visualization
Authors: Xue Chengsen , Cuomo Joanne , Meyers Walter , Closkey Thomas W. Mc 
Published: July 2017

Abstract
Flow cytometric assessment of cellular and intracellular biomarkers facilitates the development of new classes of cancer immunotherapy therapeutics. This powerful tool has multiple applications including 1) detecting PD1, PDL-1 and caspase-3 for apoptosis, 2) isolating, defining, and quantifying dendritic cells and their intracellular cytokine profile, 3) immunophenotyping subpopulations of B, T, NK, regulatory T, and helper T cells, and, 4) using tetramer analysis to detect and monitor the frequency of antigen-specific cytotoxic T lymphocytes (CTL). However, lack of knowledge of normal distributions and standard ranges for the esoteric reportables generated by flow cytometry is one of the most challenging problems in this promising field.
Here we describe a new method to improve data quality in clinical research by big data analytics and data visualization. Each data point was tagged. By applying a simple statistical analysis, a self-defined range allowed all of the outlier numbers to be identified. By repeating this process, clear patterns emerged, and all questionable data points were marked. In addition, the system can differentiate biodiversity in subjects from a more homogenous population, which can be exploited further for the purpose of personal and precision medicine. Other benefits of the new system are to predict the outcome of the clinical study and to generate new clues in the understanding of the underlying biological mechanisms.
Big data analytics and data visualization show unparalleled advantages in oncology studies through simultaneously monitoring unlimited data points related to surface and intracellular biomarkers. It opens a new avenue in cost saving for long, time-consuming clinical trials by using all available data to detect a status change of the immune system. With the improvement of data quality, big data analytics has become an essential tool and an integrated part of cancer immunotherapy and the development of cancer vaccines.
Citation Format: Chengsen Xue, Joanne Cuomo, Walter Meyers, Thomas W. Mc Closkey. Improving data quality in oncology immunotherapy clinical research by big data analytics and data visualization [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2605. doi:10.1158/1538-7445.AM2017-2605
Abstract 2618: Agonist antibodies targeting OX40 and GITR enhance the activity of the IDO1-selective inhibitor epacadostat in preclinical models
Authors: Koblish Holly K. , Horton Brendan , Hansbury Michael , O'Connor Sybil , Lasky Kerri , Stevens Christina , Condamine Thomas , Hall Leslie , Wang Liang-Chuan , Zhang Yue , Nastri Horacio , Hollis Gregory , Huber Reid , Gajewski Thomas , Scherle Peggy 
Published: July 2017

Abstract
The majority of immunotherapeutic agents developed thus far either attempt to stimulate a more productive anti-tumor immune response or to inhibit key proteins in the immunosuppressive tumor milieu. PD-1/PD-L1 axis blockade, CTLA-4 blockade and IDO1 inhibition are examples of the latter approach and have been utilized to reverse the suppressive tumor microenvironment, resulting in clinical benefit for cancer patients. Recent clinical and preclinical data have also demonstrated that combining these approaches results in enhanced therapeutic benefit. Notably, the IDO1-selective inhibitor epacadostat has been shown to increase the efficacy of two checkpoint inhibitors, the anti-CTLA-4 antibody ipilimumab and the anti-PD-1 antibody pembrolizumab, in patients with melanoma. Because both checkpoint receptors and IDO1 serve as negative regulators of the immune response, we also explored the ability of IDO1 inhibition to combine with agents that directly activate T cells through costimulatory receptors of the tumor necrosis factor receptor (TNFR) superfamily. Rodent active surrogate agonist antibodies to 4-1BB, OX40 and GITR were tested with epacadostat in multiple preclinical models. In the B16-SIY melanoma model that does not express IDO1 in tumor cells, both epacadostat and anti-OX40 had little effect, but the combination resulted in enhanced efficacy. This was associated with increased infiltrates of CD8+ T cells and decreased numbers of FoxP3+ TILs. Increased numbers of SIY-reactive T cells were found in both the tumor and the TDLN post-therapy. In contrast, epacadostat did not provide any enhancement to the activity seen with 4-1BB. Clear combinatorial effects were seen with anti-GITR and epacadostat in the more inflamed, IDO1-expressing PAN02 pancreatic cancer model. These data suggest that IDO1 inhibition can be effective in combination with agents that agonize T cell costimulatory receptors as well as with agents that block coinhibitory receptors.
Citation Format: Holly K. Koblish, Brendan Horton, Michael Hansbury, Sybil O'Connor, Kerri Lasky, Christina Stevens, Thomas Condamine, Leslie Hall, Liang-Chuan Wang, Yue Zhang, Horacio Nastri, Gregory Hollis, Reid Huber, Thomas Gajewski, Peggy Scherle. Agonist antibodies targeting OX40 and GITR enhance the activity of the IDO1-selective inhibitor epacadostat in preclinical models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2618. doi:10.1158/1538-7445.AM2017-2618
Abstract 262: Analysis of demographics, survival and patterns of care of pediatric glioblastoma using National Cancer Database
Authors: Thakkar Jigisha , Liu Meng , Dressler Emily Van Meter , Villano John L. 
Published: July 2017

Abstract
Background
We analyzed the largest clinical database in the United States, the National Cancer Database (NCDB), comprising over 70% of cases diagnosed and/or treated at commission on Cancer approved institutions. We analyzed current hospital-based epidemiologic frequency, survival and patterns of care of pediatric glioblastoma (GBM).
Methods
Cases included patients 0-19 years between 1998-2011. Inclusion criteria for histology codes included for GBM 9440, 9441 and 9442 (9440 (GBM), 9441(Giant Cell) and 9442 (Sarcomatas component) and tumor sites (C70.0-C72.9, C75.1-C75.3) related to the brain: brain stem, cerebellum, cerebrum, ventricle and brain not otherwise specified (NOS). Kaplan-Meier survival estimates were calculated for each demographic criteria and treatment plan and Cox proportional hazards models were employed to assess the risk of mortality. Demographic variables analyzed were age, gender, race, Hispanic origin, income, education, region and insurance status. Comparisons were made among histologic subtypes and primary site.
Results
1173 patients with GBM from age 0 to 19 years were identified from 1998 to 2011 in the United States, of which 21.5%, 24.5% and 54.0% were in age group 0-5, 6-10 and 11-19 years old. The largest group (48%) received advanced care including a combination of radiation (XRT), chemotherapy and surgery. On the other hand, the no treatment group was the smallest comprising of 4% cases. 14% received surgery only, 8% received a combination of XRT and surgery and 9% received a combination of XRT and chemotherapy.
Patients that received combination of XRT, chemotherapy and surgery had significantly improved survival when compared to those without any treatment (p = 0.0048). Patients that received surgery or chemotherapy had significantly improved survival as compared to patients that did not receive the above treatments (p = 0.0027).
Conclusion
We report an extensive demographic and survival analysis of pediatric GBM. Observed difference likely reflect biology across age, gender, race and origin groups. Our analysis demonstrates concern in the delivery of optimal care to a large percentage of pediatric patients. These treatments include surgery and chemotherapy that have demonstrated survival benefits. Adverse effects of chemotherapy and XRT can limit the appropriate administration of treatment.
Citation Format: Jigisha Thakkar, Meng Liu, Emily Van Meter Dressler, John L. Villano. Analysis of demographics, survival and patterns of care of pediatric glioblastoma using National Cancer Database [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 262. doi:10.1158/1538-7445.AM2017-262
Abstract 2621: Microsatellite instability is a potential biomarker for immune checkpoint inhibitor in endometrial cancer
Authors: Yamashita Hitomi , Nakayama Kentaro , Ishikawa Noriyoshi , Minamoto Toshiko , Ishibashi Tomoka , Nakamura Kohei , Sanuki Kaori , Ono Ruriko , Ishikawa Masako , Isobe Takeshi , Kyo Satoru 
Published: July 2017

Abstract
[Introduction] In recent years, tumor cells have immune escape mechanism and immune checkpoint inhibitor therapy (anti PD-1/ PD-L1 antibody) has shown benefit in various cancers. Somatic mutations have the potential to encode ‘’non-self’’immunogenic antigens and lymphocytes infiltrate tumor cells in Microsatellite-instable (MSI) endometrial cancers. Therefore, immune checkpoint inhibitor therapy might be effective in MSI endometrial cancers.
[Method] Mismatch repair protein (MLH1, PMS2, MSH2, and MSH6), tumor-infiltrating lymphocytes (CD8), and PD-1/PD-L1 expression were assessed by immunohistochemistry in 60 patients with endometrial cancer. We examined whether MSI status have enhanced immune microenvironment and become the therapeutic effect predictor of PD-1/PD-L1 immunotherapy in endometrial cancer.
[Results] Loss of mismatch repair protein (MSI group) was identified in 8 (13.3 %) of 60 patients with endometrial cancer. Expression of tumor-infiltrating lymphocytes (CD8) and PD-L1/PD-1 were significantly higher in MSI group compared to MSS group (p=0.001, p=0.044 and p=0.013).
[Conclusion]These results suggested that immune checkpoint inhibitor (anti PD-1/PD-L1 antibody) is effective in endometrial cancers with MSI. MSI testing is likely to be a biomarker for PD-1/PD-L1 immunotherapy in endometrial cancer.
Citation Format: Hitomi Yamashita, Kentaro Nakayama, Noriyoshi Ishikawa, Toshiko Minamoto, Tomoka Ishibashi, Kohei Nakamura, Kaori Sanuki, Ruriko Ono, Masako Ishikawa, Takeshi Isobe, Satoru Kyo. Microsatellite instability is a potential biomarker for immune checkpoint inhibitor in endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2621. doi:10.1158/1538-7445.AM2017-2621
Abstract 2625: Clinicopathological features of programmed cell death ligand 1 (PD-L1) expression in resected non-small cell lung cancers
Authors: Ohhara Yoshihito , Kinoshita Ichiro , Tomaru Utano , Hatanaka Kanako C. , Hatanaka Yutaka , Honma Rio , Takeuchi Satoshi , Shimizu Yasushi , Kaga Kichizo , Matsuno Yoshihiro , Dosaka-Akita Hirotoshi 
Published: July 2017

Abstract
Background: Antibodies against programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) have recently demonstrated a survival benefit in several types of cancer, including melanoma and non-small cell lung cancer (NSCLC). PD-L1 expression has provided a predictive biomarker for anti-PD-1/PD-L1 therapy. However, the relationship between PD-L1 expression and clinical and clinicopathological characteristics remains unclear in NSCLCs. The aim of this study was to investigate the relevance of PD-L1 expression to clinical and clinicopathological factors in resected NSCLCs. Materials and Methods: PD-L1 expression was evaluated in 154 surgically resected NSCLC specimens by immunohistochemistry (IHC) using the SP142 antibody. Before the IHC of clinical samples, we performed a concordance study of Western blot analysis and IHC in 17 lung cancer cell lines. We evaluated the relationship between PD-L1 expression and clinical and clinicopathological factors by univariate and multivariate analyses. Survival curves were estimated by the Kaplan-Meier methods, and differences in survival distributions were evaluated by the log-rank test.
Results: PD-L1 expression was well concordantly observed in Western blot analysis and IHC in the lung cancer cell lines analyzed. PD-L1 expression was observed in 51 of 154 (33%) surgically resected NSCLCs. PD-L1 expression was significantly correlated with male, heavy smoking history, squamous cell carcinoma, and moderate/poor differentiation of tumors by univariate analysis. In multivariate analysis, tumor differentiation had a strong relationship with PD-L1 expression (odds ratio: 6.32, 95% CI: 1.70-23.49, P = 0.006). The survival was not statistically different between patients with high and low PD-L1 expression (5-year survival rate: 44.1% versus 58.1%, P = 0.22). PD-L1 expression was not an independent prognostic factor in univariate and multivariate analyses.
Conclusion: PD-L1 expression was strongly associated with tumor differentiation in resected NSCLCs. PD-L1 expression was not a prognostic factor in this cohort of resected NSCLCs.
Citation Format: Yoshihito Ohhara, Ichiro Kinoshita, Utano Tomaru, Kanako C. Hatanaka, Yutaka Hatanaka, Rio Honma, Satoshi Takeuchi, Yasushi Shimizu, Kichizo Kaga, Yoshihiro Matsuno, Hirotoshi Dosaka-Akita. Clinicopathological features of programmed cell death ligand 1 (PD-L1) expression in resected non-small cell lung cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2625. doi:10.1158/1538-7445.AM2017-2625
Abstract 263: Epidemiology of primary lung cancer and its trend northeast of Iran during 1985-2012
Authors: Salehi Maryam , Shojaee Pardis , Shahidsales Soodabeh , Aledavood Seyed Amir , Seilaniantoosi Mehdi , Goshayeshi Golboo , Khoshroo Fahimeh 
Published: July 2017

Abstract
Introduction: In this study we investigated epidemiology and trends of primary lung cancers in northeast of Iran during 1985-2012.
Methods: In this cross-sectional study records of primary lung cancers from 1985 to 2012 in Mashhad, northeast of Iran, were investigated. Data were obtained from the referral oncologic hospital and private radiation oncology clinic. To study trends, the duration of study was categorized into three periods: 1985-1995, 1995-2005 and 2005-2012. Statistically significant level was considered &lt;0.05.
Results: Of 939 cases with mean age of 60.57 (±12.31) years, 660(70.3%) were male. Male to female ratio was 2.36. Mean age was 61.47±12.01 years for males and 58.45±12.75 for females (p=0.001). Mean age at diagnosis and rate of smokers was unchanged in three intervals (table 1).
Time period1985-19951995-20052005-20012P valueAge(years)60.67±11.7460.57±12.2460.49±12.940.98Gender:Male167(78.4)330(68.6)163(66.5)0.01female46(21.6)151(31.4)82(33.5Male to female ratio3.632.181.99Smoking history:Yes69(76.7)211(67.8)100(65)0.15no21(23.3)100(32.2)54(35)Smokers:Male59(85.5)159(75.4)74(74)0.16Female10(14.5)52(24.6)26(26)Male-to-female ratio of smokers5.93.062.84
Squamous cell carcinoma with relative frequency of 44.2% was the most frequent pathologic subtype in total population followed by adenocarcinoma (18.2%), Small Cell Lung cancer (16.8%), large Cell carcinoma (1.3%) and other subtypes (19.5%). Relative frequency of pathologic subtypes had significant changes in three intervals (p &lt;0.001). Relative frequency of adenocarcinoma and large cell carcinoma were increasing while it was decreasing for SCC and SCLCs during three recent decades. There was statistically significant difference in mean age at diagnosis (p&lt;0.001), rate of smokers (p&lt;0.001) and male to female ratio (p=0.01) between four leading pathologic subtypes. Mean age at diagnosis (55.92±12.90 years), male to female ratio (1.69), and rate of smokers (46.8%) were lowest in adenocarcinomas.
Conclusion: Similar to universal picture, adenocarcinoma showed increasing rates during recent three decades with higher prevalence among younger aged patients, women and nonsmokers. These trends are indicative of changes in exposures and smoking habits and reveal the need for regional studies in this context.
Citation Format: Maryam Salehi, Pardis Shojaee, Soodabeh Shahidsales, Seyed Amir Aledavood, Mehdi Seilaniantoosi, Golboo Goshayeshi, Fahimeh Khoshroo. Epidemiology of primary lung cancer and its trend northeast of Iran during 1985-2012 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 263. doi:10.1158/1538-7445.AM2017-263
Abstract 2652: Favorable outcome of primary mediastinal large B-cell lymphoma treated by Dose Adjusted EPOCH-Rituximab regimen
Authors: Grifi Fatiha , Bougherira Soraya 
Published: July 2017

Abstract
Background Primary Mediastinal Large B-Cell Lymphoma (PMLBCL) is a unique type of B-cell lymphoma probably arising from a putative thymic medulla B-cell. One to 2% of NHL, 7% of all diffuse large B-cell lymphomas (DLBCL), occurring more often in young females. Often presents with superior vena cava syndrome and airway compromise. Treatment is with chemotherapy combined with Rituximab, followed by involved field radiation therapy to mediastinum. PMLBCL has better outcome than others DLBCL. We aimed to develop a more dose-dense/intense regimens that improves the rate of cure with an attempt to avoid mediastinal radiation. Patients and methods A prospective study was conducted in our department from January to December 2015, in 6 patients with untreated primary mediastinal B-cell lymphoma. An infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) has been administred according to the protocol Day 1 : Rituximab 375 mg/m2 IV Day 1-4 : Etoposide 50 mg/m2 IV, Doxorubicin 10 mg/m2 AND Vincristine 0.4 mg/m2 Day 5 : Cyclophosphamide 750 mg/m2 Days 1-5 : Prednisone 60 mg/m2 PO BID. Administer G-CSF 5 mcg/kg SQ on day 6 until ANC exceeds nadir Cycles were repeated every 3 weeks for a toal of 6 cycles Results The median age of the patients was 32 years, the male to female ratio : 2:4. Systemic symptoms mainly fever and weight loss, were present in all cases; increased LDH levels were also observed in 50% of cases. Majority of the patients (83%) presented with stage I/II disease, bulky mass with a median tumor diameter 15 cm. Most had features of local extension like pleuro-pericardial effusion. Absence of infradiaphragmatic lymph nodes and no bone marrow involvement at presentation. All patients required biopsy from the mediastinal mass by image guided core biopsy. The patients were treated by RDA-EPOCH, they received 4 to 6 courses, without involved field radiotherapy (only one patient underwent radiotherapy for residual mass). No late morbidity or cardiac toxic effects were found in any patients. After 24 months of follow-up, one patient still received treatment and was not evaluable. 5 patients achieved complete remission and were disease-free at the last visit. Conclusion PMBCL is a specific lymphoma entity seen in the young with good survival. It has a distinct clinical behavior and prognosis, and therefore require a different therapeutic approach. The R/DA-EPOCH regimen need to be confirmed in further prospective study for a large cohort.
Note: This abstract was not presented at the meeting.
Citation Format: Fatiha Grifi, Soraya Bougherira. Favorable outcome of primary mediastinal large B-cell lymphoma treated by Dose Adjusted EPOCH-Rituximab regimen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2652. doi:10.1158/1538-7445.AM2017-2652
Abstract 266: Trends in age distribution of breast cancer, in north east of Iran: Report of six thousand patients over 30 years
Authors: Salehi Maryam , Shahidsales Soodabeh , Seilaniantousi Mehdi , Noferesti Gholamhosein , Salehi Mahta , bajgiran Amirhossein mohammadian 
Published: July 2017

Abstract
Aim: This study was aimed to evaluate the age at the time of diagnosis of breast cancer and it’s probably changes in distribution among patients during 30 years.
Methods: This cross- sectional study was conducted in Mashhad, Iran from 1981 until 2011. The data of patients were obtained from case records. The duration of study was categorized into three periods: 1981-1990, 1991-2000 and 2001-2011. SPSS software was used for analyses. The difference was considered significant if P&lt;0.05.
Result: From 6274 breast cancer cases, 174 patients were male (2.5%) and the others 6100 were female (97.5%).Mean age at the time of diagnosis was 49.07 ± 12.07 years (male: 56.48 ± 14.14, female: 48.8 ±12.01). There was significant difference in age by sex (p &lt;0.001). Table 1 presents the mean age of studied patients in each 10 years of study. ANOVA test showed that there was not statistical significant difference (P value= 0.1).
DecadesFrequencyMean ageSDYoungestOldest1981-199046747.9712.04318882000-1991177149.0312.33820992001-2011394949.2211.9542098
The most histologic type of breast cancer was ductal carcinoma 65.6% others percent in order were: NOS 19.6%, lobular 3.7%, medullary 2.8%, adenocarcinoma 2.8%, tubular and papillary 0.2% and 5.1% of other types. Relative frequency of histologic types had significant differences among 3 intervals (p &lt;0.001), the frequency of adenocarcinoma was decreasing but ductal carcinoma was increasing during 3 decades. Mean age of ductal carcinoma, lobular, medullary and adenocarcinoma was 48.9±11.8, 50.6±12.4, 46.4±11.4, 50.2±11.9, respectively. Mean age had significant differences among these main histologic types (p =0.002).98% of patients were urban and 2% were rural. Mean age of these 2 groups has statistical significant difference (P = 0.001) and is 10 years older in rural patients. Frequency of people who live in urban area was increased significantly (p&lt;00.1) during these 30 years compare with rural area.
Conclusion: breast cancer occurs in Iranian women at least one decade younger than women in developed countries we found no change in mean age of diagnosis of breast cancer during these 30 years from 1981 to 2011.
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Note: This abstract was not presented at the meeting.
Citation Format: Maryam Salehi, Soodabeh Shahidsales, Mehdi Seilaniantousi, Gholamhosein Noferesti, Mahta Salehi, Amirhossein mohammadian bajgiran. Trends in age distribution of breast cancer, in north east of Iran: Report of six thousand patients over 30 years [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 266. doi:10.1158/1538-7445.AM2017-266