bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3698: The landscape of published cancer meta-analyses: a descriptive look from 2008-2013
Authors: Qadir Ximena V. , Clyne Mindy , Lam Tram K. , Khoury Muin J. , Schully Sheri D.
Published: August 2015

Cancer epidemiology has undergone rapid growth in the past two decades. This rapid expansion of scientific literature in cancer epidemiology has required scientists to increasingly look towards meta-analyses to help navigate the “sea of literature”. Knowledge integration has facilitated the movement of translation of scientific findings into clinical applications, evidence-based recommendations and population health impact. Performing meta-analysis has allowed scientists to filter through large datasets and translate these scientific or clinical findings effectively. To our knowledge, there has never been a systematic attempt to compile meta-analyses in cancer. Here, we describe the landscape of cancer meta-analyses including publication production stratified by year, cancer outcome measures, study design, cancer type, journal and country leaders in the field.

To ascertain human cancer meta-analytical studies published in the scientific literature during the years 2008 through 2013, we searched PubMed using a text query and the Human Genome Epidemiology (HuGE) Navigator. Two reviewers read through abstracts to determine whether the articles met inclusion criteria. Articles were included if there was a meta-analytical analysis of a human cancer measurement and met one of the following outcome criteria: 1) risk of disease, 2) diagnostic measure, 3) prognostic measure, 4) treatment of disease, including long-term survival and/or adverse events and 5) screening for disease. Coding of articles involved extracting information from the Medline version of each PubMed article reference (i.e. Journal title, year of publication, first author location and cancer-site mesh terms), and by manually reviewing abstracts for classification on the human cancer outcome measurement and other manually coded information.

A total of 4,007 cancer meta-analyses were captured by PubMed from 2008 to 2013. Our systematic review of cancer meta-analyses publications indicates a rapid growth of cancer meta-analyses worldwide with 20% production in the past 6-year time period. Furthermore, PLoS One and Asian Pacific Journal of Cancer Prevention were recorded as the top two publishers in the research field. Genomic, clinical and modifiable cancer risk factors were captured as the top leading cancer meta-analyses studies. Observational studies were captured as the leading meta-analyses study design. In the past five years there was an increased wide distribution of meta-analyses on all cancer types.

Citation Format: Ximena V. Qadir, Mindy Clyne, Tram K. Lam, Muin J. Khoury, Sheri D. Schully. The landscape of published cancer meta-analyses: a descriptive look from 2008-2013. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3698. doi:10.1158/1538-7445.AM2015-3698
Abstract 3701: Health disparity characteristics on growth patterns of breast cancer mortality trends among the US Counties, 1989-2010
Authors: Yoo Wonsuk , Rust George , Zhang Shun , Lillard James
Published: August 2015

Background: Group-based trajectory models are increasingly being applied to address questions related to the development of cancer mortalities over time and, more recently, there is a need to move away from the interpretation of trajectory groups as distinct entities. In this study, we aim to identify trajectory-patterns which have distinct epidemiologic disparity among US counties, and to assess whether health disparities in the socioeconomic characteristics are associated with a greater women health burden in breast cancer.

Methods: Cases of breast cancer diagnosed between 1989 and 2010 were selected from Center for Disease Control's WONDER Online Databases using International Classification of Diseases for Malignant neoplasm of breast (ICD 10 - C50). Age-adjusted mortality rates of breast cancer between 1989 and 2010 were calculated by counties as well as race (African American and White). Growth patterns were identified using Growth Mixture Modeling (GMM) method and disparity characteristics including socioeconomic attributes were investigated through National Cancer Institute's Surveillance Epidemiology and End Results (SEER) County Attributes Dataset.

Results: We identified the following three growth sub-patterns in the trajectories of breast cancer mortality rates between 1989 and 2010 among US counties: (1) a majority (61%) following a gradual decreasing trajectories, (2) a non-decreasing trajectories (31%), and the remainder following a trajectory with relatively rapid decreasing (7%). We compared disparity characteristics of education level, median household income, poverty percentage, percentages of older ages (65+) and younger ages (<18), and rural-urban continuum among above three sub-patterns.

Conclusions: There is heterogeneity of the socioeconomic characteristics that are highly associated with growth patterns in trajectories of breast cancer mortality rates. Growth mixture models are an effective tool to be able to capture health disparities in heterogeneity among counties in the trajectory of breast cancer mortality.

Note: This abstract was not presented at the meeting.

Citation Format: Wonsuk Yoo, George Rust, Shun Zhang, James Lillard. Health disparity characteristics on growth patterns of breast cancer mortality trends among the US Counties, 1989-2010. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3701. doi:10.1158/1538-7445.AM2015-3701
Abstract 3703: A prospective study of racial/ethnic disparities in pain experience among breast cancer patients undergoing radiotherapy
Authors: Lee Eunkyung , Takita Cristiane , Wright Jean L. , Reis Isildinha M. , Zhao Wei , Hu Jennifer J.
Published: August 2015

Purpose: Pain is one of the multiple quality of life issues in breast cancer survivors. We sought to determine whether race/ethnic disparity exists in radiotherapy (RT)-induced pain and to assess associated risk factors.

Methods and Materials: Consecutive 375 female patients undergoing adjuvant RT after breast-conserving surgery during 2009-2014 were evaluated. Pain score was assessed as mean of the four pain severity items (pain at its worst, least, average, and now) using 11-point numeric rating scale (0-10) at pre-RT and post-RT. Pain scores of 4 to 10 were regarded as clinically relevant pain. Pain presence and RT-induced change were examined. In multivariable logistic regression analysis, we evaluated risk factors for pre-RT, post-RT, and RT-induced pain.

Results: A total of 15.5% participants self-identified as non-Hispanic white (NHW), 20.8% African American (AA), and 63.7% as Hispanic white (HW). AA patients were more likely to be obese, to report comorbidities, and to have advanced diseases. Pain prevalence was 15.9% at pre-RT and 31.3% at post-RT while 19.7% of patients experienced RT-induced pain. Post-RT pain severity and pain presence were associated with race/ethnicity, age, BMI, number of comorbidity, tumor stage, HER2 status, axillary surgery, fractionation, RT dose, breast volume, and hotspot volume (V105). Multivariable analyses identified HW and obese as independently associated with pre-RT pain while AA, HW, younger age (<50), number of comorbidity (≥2), V105, and pre-RT pain score with post-RT pain. Multivariable analysis also identified AA (OR = 3.23; 95% CI = 1.05-9.93, p = 0.041), younger age (OR = 2.45, 95% CI = 1.24-4.85, p = 0.010), and number of comorbidity (OR = 3.05, 95% CI = 1.29-7.21, p = 0.011 for 2; OR = 4.58, 95% CI = 1.46-14.37, p = 0.009 for at least 3) as risk factors for RT-induced pain.

Conclusions: This prospective study demonstrates AA and younger women are more susceptible to RT-induced pain. In addition, the management of comorbidity conditions, such as diabetes, hypertension, and thyroid disease, deserves attention to prevent RT-induced pain in breast cancer patients.

Citation Format: Eunkyung Lee, Cristiane Takita, Jean L. Wright, Isildinha M. Reis, Wei Zhao, Jennifer J. Hu. A prospective study of racial/ethnic disparities in pain experience among breast cancer patients undergoing radiotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3703. doi:10.1158/1538-7445.AM2015-3703
Abstract 3709: Second cancers following Waldenström macroglobulinemia/lymphoplasmacytic lymphoma in the United States: analysis of Surveillance, Epidemiology and End Results (SEER) registry data, 1992 - 2011
Authors: McMaster Mary L. , Goldin Lynn R. , Caporaso Neil E.
Published: August 2015

Waldenström macroglobulinemia (WM) is a subtype of lymphoplasmacytic lymphoma (LPL) that features secretion of monoclonal immunoglobulin type M (IgM) in the blood. WM/LPL occurs most commonly in elderly (median, 73 years) white males and is characterized by an indolent course and relatively long survival. Thus, WM/LPL patients may be at risk for development of subsequent cancers. We used data from the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) program to evaluate the risk of subsequent primary cancer in more than 3800 patients diagnosed with WM or LPL during the 20-year period, 1992 - 2011. We calculated observed-to-expected (O/E) standardized incidence ratios, together with 95% confidence intervals (95%CI), for invasive cancers occurring in these individuals. We found that the overall risk for second cancers was significantly increased among survivors of WM/LPL (O/E = 1.49; 95%CI 1.37-1.62) and risk increased with time since diagnosis. Increased risk was observed for both solid tumors (O/E = 1.21; 95%CI 1.09-1.33) and hematolymphoid cancers (O/E = 4.20; 95%CI 3.54-4.95). Significantly increased site-specific risks were seen for cancers of the lung and bronchus, melanoma, non-epithelial skin, and thyroid as well as for Hodgkin and non-Hodgkin lymphoma, multiple myeloma, and acute myeloid leukemia. Sample size limited subset analysis; however, overall increased risk was observed in all race (white, black, Asian/Pacific Islanders) and gender categories except for Asians/Pacific Islanders. Risk for second cancers appeared greater in younger patients (<65 vs. 65+) as well as in those diagnosed more recently, which may reflect changes in treatment regimens over time. We conclude that host factors, shared exposures and treatment effects may play a role in these observations.

Citation Format: Mary L. McMaster, Lynn R. Goldin, Neil E. Caporaso. Second cancers following Waldenström macroglobulinemia/lymphoplasmacytic lymphoma in the United States: analysis of Surveillance, Epidemiology and End Results (SEER) registry data, 1992 - 2011. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3709. doi:10.1158/1538-7445.AM2015-3709
Abstract 3711: The decrease in global cancer mortality
Authors: Boffetta Paolo
Published: August 2015

Background: A decrease in cancer mortality has been reported in the United States, Europe and other developed regions of the world during the last two decades. Whether similar trends apply to less-developed countries - and globally - is unclear.

Methods: We aimed to describe the global patterns of cancer mortality by conducting a systematic analysis of the WHO mortality database for countries for which high- or intermediate-quality data on death certifications are available for a period of at least 10 years (typically 2003-2012). We included 60 countries in the analysis, and calculated age-specific and age-adjusted mortality rates.

Results: A decrease in overall cancer mortality of approximately 1% per year was present in both developed and less-developed regions, and in both genders. For cancers of the esophagus, stomach, larynx and thyroid, the average decrease in global mortality rate was greater than 2% per year. Individual cancers which showed an increase in mortality rates on a global scale are limited to pancreas and brain (both genders), lung (women), melanoma and kidney (men) and endometrium.

Conclusions: Reasons for the decrease in cancer mortality in less-developed countries may include decrease in cancer incidence, shift in the stage distribution, shift in the proportional contribution of individual cancers, and improved therapy. The increase in the number of cancer deaths, globally and in less-developed countries, is primarily driven by changes in the demographic structure of the population, but the risk of the individual of dying from cancer appears to decrease in all countries with reliable data. Cancers with increasing mortality rates should be given priority for research.

Citation Format: Paolo Boffetta. The decrease in global cancer mortality. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3711. doi:10.1158/1538-7445.AM2015-3711
Abstract 3712: Incidence trend of NPC using age-period-cohort analysis from1987 to 2011 in Sihui County, southern China
Authors: Liu Qing , Cao Sumei , Huang Qihong , Zhang Lifang , Li Yanhua , Xie Shanghang
Published: August 2015

In the past several decades, declining incidence rates of NPC have been observed in Chinese populations in Hong Kong, Taiwan, Los Angeles, and Singapore.However, the incidents rates in southern China have remained stable.This study describes the incidence trend of nasopharyngeal carcinoma (NPC) using age-period-cohort (APC) analysis from 1987 to 2011 in Sihui County, southern China. Age-standardized incidence rates compared with the world standard population were examined in both males and females. A Joinpoint regression analysis was conducted to quantify the changes in incidence trends. A Poisson regression APC model was used to assess the age, period, and birth cohort effects on incidence. Age-standardized incidence rates during the study period were 30.29 and 13.09 per 100,000 for males and females, respectively. The incidence rates of NPC remained stable with a non statistical significant average annual percentage change of 0.2% for males and -1.6% for females throughout the entire period. A statistically significant increase (estimated annual percentage change, 6.8%; 95% confidence interval, 0.1%-14.0%) was observed from 2003 to 2009 for males. The incidence of NPC increased with advancing age up to ages 50-59 and decreased at ages >60 years. The curves of NPC incidence by period were virtually flat for males and females. The curve for males by birth cohort showed an increase from the 1922 to 1952 cohort and a decrease thereafter. In females, there was an undulating increase in relative risks from the 1922 to 1972 cohort. In conclusion, the incidence trends for NPC remained generally stable in Sihui from 1987 to 2011, with an increase during 2003-2009. The relative risks of NPC increased in younger female cohorts, the underlying reason of which is expected to be further explored.

Note: This abstract was not presented at the meeting.

Citation Format: Qing Liu, Sumei Cao, Qihong Huang, Lifang Zhang, Yanhua Li, Shanghang Xie. Incidence trend of NPC using age-period-cohort analysis from1987 to 2011 in Sihui County, southern China. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3712. doi:10.1158/1538-7445.AM2015-3712
Abstract 3718: Trends in tobacco use and prostate cancer mortality in four US states, 1999-2010
Authors: Jones Miranda R. , Joshu Corinne E. , Kanarek Norma F. , Navas-Acien Ana , Richardson Kelly A. , Platz Elizabeth A.
Published: August 2015

Background: In the US, prostate cancer mortality rates have declined in past decades. Cigarette smoking, a risk factor for prostate cancer death, has also declined. It is unknown whether declines in smoking prevalence produced detectable declines in prostate cancer mortality in the population.

Objective: To examine prostate cancer mortality rates in relation to changes in tobacco use in the population.

Methods: We studied men ≥35 years of age from California, Kentucky, Maryland and Utah. State smoking prevalences were obtained from the Behavioral Risk Factor Surveillance System (BRFSS). Mortality rates for prostate cancer and external causes, as a control condition, were obtained from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) system. The average annual percent change for smoking and prostate cancer mortality for 1999 to 2010 was estimated using joinpoint analysis.

Results: In 1999, the smoking prevalence among men ≥35 years of age was 31.7%, 20.9%, 19.9% and 14.8% in Kentucky, Maryland, California and Utah, respectively. Between 1999 and 2010, smoking in Kentucky declined by 3.0% per year (95% CI: -4.0%, -1.9%) and prostate cancer mortality declined by 3.5% per year (95% CI: -4.3%, -2.7%). In Maryland, smoking declined non-significantly by 3.0% per year (95% CI: -7.0%, 1.2%) and prostate cancer mortality declined by 3.5% per year (95% CI: -4.1%, -3.0%). In California, smoking declined by 3.5% per year (95% CI: -4.4%, -2.5%) and prostate cancer mortality declined by 2.5% per year (95% CI: -2.9%, -2.2%). In Utah, smoking declined by 3.5% per year (95% CI: -5.6%, -1.3%) and prostate cancer mortality declined by 2.1% per year (95% CI: -3.8%, -0.4%). No such patterns were observed for smoking and external causes of death in any of the states.

Conclusion: Similar declines were observed in the prevalence of smoking and prostate cancer mortality. Although ecological, this study suggests that declines in prostate cancer mortality rates are consistent with a beneficial effect of reducing tobacco use at the population level.

Citation Format: Miranda R. Jones, Corinne E. Joshu, Norma F. Kanarek, Ana Navas-Acien, Kelly A. Richardson, Elizabeth A. Platz. Trends in tobacco use and prostate cancer mortality in four US states, 1999-2010. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3718. doi:10.1158/1538-7445.AM2015-3718
Abstract 3721: Rapid widening of age and race health disparities in prostate cancer outcomes within the United States, 1973-2014
Authors: Lawrence Richard J. , Urban Damien , Golan Talia , Saad Akram , Berger Raanan , Leibowitz-Amit Raya , Bar Jair , Den Robert , Goldstein Jeffrey , Symon Zvi
Published: August 2015

Introduction

Little is known concerning how cancer-outcome disparities have changed over time. We investigated how age and race disparities in prostate cancer (PCa) survival have changed in the USA over the last 40 years.

Methods

We utilized the SEER database to track PCa outcomes. Incl. criteria: subjects with PCa diagnosed 1973 - 2008, aged 50-89 yrs. Excl. criteria: multiple primary cancers, unknown stage.

Results

658,916 PCa patients were analyzed. Median follow up for alive patients was 54m (interquart. range 39-75m). Median age of diagnosis decreased from 73 to 60 yrs from 1973 to 2008, and the proportion aged > = 70 yrs decreased from 62% to 40%. The proportion diagnosed with metastatic disease decreased from 18% to 4%; likewise amongst those with M0 disease the proportion with T3-4 decreased from 41% to 17%. The remainder of the results are confined to M0 disease. Four-year cancer specific death decreased progressively for all age groups. But whereas 4 year cancer specific mortality dropped from 24% to 3% in those aged 50-54, it only decreased from 38% to 18% in those aged 85-89. Whereas the hazard ratio (HR) for cancer-specific death for those aged 85-89 (50-54 year old subjects reference group) was 1.6 in 1973-9, in 2000-8 it was 10.9 (table). The widening age disparities were only marginally altered by incorporation of ‘tumor stage’ into the model. Similar widening age disparities were seen in metastatic disease. Race-related disparities also widened over the study period; the HR for death increasing from 1.1 (1973-79) to 1.3 (2000-8).

Hazard ratios for prostate cancer-specific death stratified by year of diagnosis, stage M0Age1973-91980-91990-92000-950-4111155-91.11.01.11.060-41.11.11.51.265-91.11.11.81.670-41.21.22.22.375-91.21.32.93.580-41.41.53.86.185-91.61.75.010.9

Conclusions

Age- and Race- related health disparities in survival outcomes in both metastatic and non-metastatic prostate cancer have greatly widened over the past 40 years; this effect appears to be accelerating and is not explained by delayed diagnosis. Since outcome disparities have grown against a backdrop of improved screening, diagnosis and treatment, it appears that measures targeted at these populations will be needed in order to redress the imbalance.

Citation Format: Richard J. Lawrence, Damien Urban, Talia Golan, Akram Saad, Raanan Berger, Raya Leibowitz-Amit, Jair Bar, Robert Den, Jeffrey Goldstein, Zvi Symon. Rapid widening of age and race health disparities in prostate cancer outcomes within the United States, 1973-2014. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3721. doi:10.1158/1538-7445.AM2015-3721
Abstract 373: Analytical and clinical validation of an EpCAM-independent assay for CTC detection in peripheral blood of early breast cancer patients based on Cytokeratin-19 (CK-19) RT-qPCR
Authors: Strati Areti , Markou Athina , Stathopoulou Aliki , Apostolaki Stella , Mavroudis Dimitris , Georgoulias Vasilis , Lianidou Evi S.
Published: August 2015

Introduction: The aim of our study was to evaluate the prognostic significance of our previously developed EpCAM independent RT-qPCR assay for CK-19 mRNA (Stathopoulou et al, Int J Cancer 2006) and validate its analytical and clinical performance in early breast cancer.

Methods: Quality control on analytical sensitivity and specificity, linearity, intra- and inter-assay reproducibility, and stability of the external standard used for the preparation of the calibration curves was performed. Reproducibility of the assay between our labs was evaluated by analyzing 26 cDNAs. The prognostic significance of the assay in respect to DFI and OS was evaluated by analysing peripheral blood of 179 patients with stage I/II breast cancer postoperatively, before the administration of adjuvant chemotherapy.

Results: The limit of detection (LOD) is 3 copies/reaction and limit of Quantitation (LOQ) 10 copies/reaction. The linear range of the calibration curve was 10-105copies/reaction and the intra- and inter-assay reproducibility are shown below:

CK19 transcriptsReproducibility of the assay (n = 3)copies/reactionIntra-assay RSD (%)Inter-assay RSD (%)101.973.151020.932.241030.450.861040.122.581050.11.52

The inter-lab reproducibility of the assay was evaluated by analyzing 26 cDNA samples in both labs and there was a 100% concordance. During the follow up period (8 years) 32/179 (17.9%) patients relapsed and 18/179 (10%) patients died from the disease. 45/179 (25.1%) samples were found positive for CK-19 and 134/179 (74.9%) negative. In the group of CK-19 positive patients 15/45(33.3%) relapsed and 9/45(20.0%) died while in the group of CK-19 negative patients 17(12.7%) patients relapsed and 9(6.7%) died. Kaplan-Meier analysis showed that CK-19 mRNA positivity was significantly associated with DFI (P = 0.014) and OS (P = 0.051).

Conclusions: This EpCAM independent assay can be used for a high-throughput detection of CTCs in peripheral blood and has prognostic significance in early breast cancer.

Citation Format: Areti Strati, Athina Markou, Aliki Stathopoulou, Stella Apostolaki, Dimitris Mavroudis, Vasilis Georgoulias, Evi S. Lianidou. Analytical and clinical validation of an EpCAM-independent assay for CTC detection in peripheral blood of early breast cancer patients based on Cytokeratin-19 (CK-19) RT-qPCR. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 373. doi:10.1158/1538-7445.AM2015-373
Abstract 3737: Severe obesity and colorectal cancer patient survival
Authors: Daniel Carrie R. , Shu Xiang , Ye Yuanqing , Gu Jian , Raju G. S. , Kopetz Scott , Wu Xifeng
Published: August 2015

Background: More than one-third of all U.S. adults are obese (BMI >30); and 15% of middle-aged adults, the group most commonly diagnosed and treated for colorectal and other cancers, meet the criteria for class II obesity (BMI> = 35). In contrast to the large and consistent body of evidence for obesity and increased colorectal cancer risk, several recent meta-analyses indicate that the association with colorectal patient survival is poorly defined. Some evidence suggests that moderate adiposity may be protective. In a prospective cohort of well-characterized CRC patients, we evaluated class I and class II obesity in relation to 5-year and 10-year survival outcomes.

Methods: Histologically-confirmed colorectal adenocarcinoma patients (n = 634) evaluated at the University of Texas MD Anderson Cancer Center were followed for a median period of 4 years. We collected epidemiological data through questionnaires and abstracted treatment, anthropometric, and clinicopathologic data from patients’ electronic medical records. Overall survival (OS) and progression/recurrence-free survival (PFS) were calculated from the date of pathologic diagnosis until disease progression, first recurrence, or death. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in multivariable Cox proportional hazards models adjusted for demographics, lifestyle factors, tumor characteristics, and treatment modality.

Results: We observed a 1.5-fold increased risk of death among class II obese (BMI> = 35), as compared to overweight CRC patients in multivariable-adjusted models. Among patients who reported stable weight and among stage I-III patients, the association between class II obesity and OS was more pronounced [BMI> = 35 vs. BMI 25-29.9 (ref), HR and 95% CI: 3.49 (1.68-7.22) and 2.40 (1.33-4.31), respectively], but no associations were observed among metastatic patients or among patients who experienced recent weight loss. Similar associations were observed with PFS, but few reached statistical significance.

Conclusions: Severe adiposity defined as class II obesity (BMI > = 35) was associated with significantly higher mortality among CRC patients. Clarifying what is not a healthy weight for cancer patients and survivors remains both a clinically relevant and timely concern. Understanding and targeting this relationship may improve long-term outcomes among growing numbers of obese patients and cancer survivors.

Citation Format: Carrie R. Daniel, Xiang Shu, Yuanqing Ye, Jian Gu, G. S. Raju, Scott Kopetz, Xifeng Wu. Severe obesity and colorectal cancer patient survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3737. doi:10.1158/1538-7445.AM2015-3737
Abstract 3738: Body mass, weight, and body size and uterine leiomyoma in the Korea Nurses’ Health Study
Authors: Lee Jung Eun , Lee Ji Eun , Cho Eunyoung , Jang Hee Jung , Jung Heeja , Lee Hea-Young , Kim Su , Kim Ok Soo
Published: August 2015

Background: Body mass and body size may influence uterine leiomyoma development in Asian populations.

Methods: We examined the associations of body mass index, weight change, and childhood, adolescent or current body size with history of uterine leiomyoma in the Korea Nurses’ Health Study. History of uterine leiomyoma and anthropometric factors were assessed through self-administered questionnaires. We included only women who had experienced pregnancies to avoid detection bias. As a result, a total of 5670 women were included and 560 women reported that they had uterine leiomyoma. The median age of women was 38 years. We calculated odds ratios(OR)s and 95% confidence interval (95% CI)s adjusted for potential risk factors for uterine leiomyoma.

Results: Current body mass index was associated with higher odds of having uterine leiomyomas; multivariate OR (95% CI) was 1.52(1.03-2.25; P for trend = 0.003) comparing ≥27.5 with 18.5-23 kg/m2. Body size in adulthood was associated with increased odds of having uterine leiomyomas (P for trend = 0.002), whereas childhood or adolescent body size was not. Also, women with greater change in body weight since the first year of college tended to have higher odds of having uterine leiomyomas, compared to those whose weight had been stable.

Conclusion: We found that body mass and weight gain in adulthood were associated with increased odds of having uterine leiomyoma in Korean women, but body mass in early life was not.

Citation Format: Jung Eun Lee, Ji Eun Lee, Eunyoung Cho, Hee Jung Jang, Heeja Jung, Hea-Young Lee, Su Kim, Ok Soo Kim. Body mass, weight, and body size and uterine leiomyoma in the Korea Nurses’ Health Study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3738. doi:10.1158/1538-7445.AM2015-3738
Abstract 3742: The influence of masculinity, racism, and social support on colorectal cancer screening uptake among African American men: A systematic review
Authors: Rogers Charles R. , Mitchell Jamie A. , Franta Gabriel J. , Foster Margaret J. , Shires Deirde
Published: August 2015

BACKGROUND: Colorectal cancer (CRC) is both preventable and highly treatable, yet incidence and mortality rates are 25% and 50% higher among African American men compared to their white counterparts. This disproportionate burden places African American men last among all racial/ethnic groups of both genders for age-adjusted CRC mortality rates and five-year survival rates. These disparities are well documented, yet preventive screening completion among African American men is relatively low, understudied, and poorly explicated. A growing body of literature indicates that separately, masculinity, racism, and social support are strong influences on CRC screening uptake.

METHODS: We conducted a systematic review with the purpose of identifying and synthesizing the connections between extant literature on the associations between masculinity, racism, social support, and CRC screening completion. Utilizing Garrard's Matrix Method, 19 studies met inclusion/exclusion criteria; and the methodological quality of the reviewed evidence was assessed.

CONCLUSIONS: Thirteen studies employed non-experimental research designs; a quasi-experimental design was present in four, and two utilized experimental designs. Studies were published between 2000 and 2014; the majority within five years. Preliminary qualitative synthesis suggests that social support was most frequently addressed (79%), while masculinity and racism were equally examined (11%) for their influence on CRC screening. After evaluating the conceptual and methodological characteristics of included studies, 42% fell below average in quality and rigor. The need for increased attention to the sociocultural correlates of CRC screening for African American men are highlighted in this systematic review, and important recommendations for research and practice are provided.

Citation Format: Charles R. Rogers, Jamie A. Mitchell, Gabriel J. Franta, Margaret J. Foster, Deirde Shires. The influence of masculinity, racism, and social support on colorectal cancer screening uptake among African American men: A systematic review. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3742. doi:10.1158/1538-7445.AM2015-3742
Abstract 3749: Uses and update for CellMiner, a tool for access to and comparison of molecular data and pharmacological response for the NCI-60
Authors: Reinhold William C. , Sunshine Margot , Varma Sudir , Rajapakse Vinodh , Doroshow James , Morris Joel , Pmmier Yves
Published: August 2015

Integration and understanding of genomic and proteomic data and their relationships with and influences on pharmacology have become key components of cancer research and its translation to therapeutics. Nonetheless, multiple significant obstacles need to be overcome for both their integration and understanding. The NCI-60 cancerous cell lines provide a premier opportunity in this area due to the scope and quality of the available data. CellMiner (http://discover.nci.nih.gov/cellminer) is a web-application that allows the user to rapidly access data for relative levels of transcript expression for 25,772 genes, genetic variants for 16,568 genes, transcript expression for 360 microRNAs, protein levels for 94 genes, and DNA copy number (from aCGH) for 23,413 genes. In addition, it provides concentration-response activities for 20,002 compounds including 114 Food and Drug Administration (FDA)-approved, 55 clinical trial, and 349 known mechanism-of-action drugs. Here we present our latest CellMiner update along with examples of data integration that provide enhanced understanding in the systems biological sense. Included in the tool updates are i) the upcoming “Protein mean value” cell line signature tool, ii) the recently introduced “Gene DNA copy number” tool, iii) introduction of the “Cross-correlations of transcripts, microRNAs, and drugs” tool, iv) the provision of additional forms of data in the standard output for the “Pattern comparisons” tool, and v) upgrades of the “Genetic variant versus drug visualization” tool allowing the user to query for all drugs significantly correlated to genomic variants for the whole human genome (or visa versa). Examples of data integration will include SLFN11 expression versus the activities of DNA-damaging drugs, RAS activation considering three forms of molecular data, and PTEN knockdown and pharmacological connection (also using three forms of molecular data). The data and tools are or shortly will be publicly available at CellMiner.

Citation Format: William C. Reinhold, Margot Sunshine, Sudir Varma, Vinodh Rajapakse, James Doroshow, Joel Morris, Yves Pmmier. Uses and update for CellMiner, a tool for access to and comparison of molecular data and pharmacological response for the NCI-60. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3749. doi:10.1158/1538-7445.AM2015-3749
Abstract 3760: Modeling spatial tumor growth as seen in clinical and radiological observations
Authors: Viger Louise , Draghi Clément , Denis Fabrice , Letellier Christophe
Published: August 2015

Aim:

Predicting tumour growth is a key issue in oncology for which correctly understanding underlying mechanisms is required. In order to do that, we developed a spatio-temporal mathematical model at tissue level for tumorigenesis. Our model is based on a set of four differential equations describing interactions between host, immune, tumour and endothelial cells that we recently developed for a single site. This model is spontaneously able to reproduce angiogenic switch and metastatic phenotype.

Method:

The present work is devoted to an extension onto a spatial two-dimensional Euclidean grid in which each site corresponds to approximatively ten thousand square micrometers and contains about one hundred cells. Only tumour cells can diffuse from one site to one of its eight nearest neighbors, thus corresponding to a partial differential equation with an isotropic Laplacian operator for tumour cell diffusion. Initial conditions are such as a single site located in the center of the grid contains tumour cells (all the other are tumour cells free). The tumour growth is thus obtained by integrating the differential equations using a fourth-order Runge-Kutta scheme.

Results:

Since we explicitly considered endothelial cells, our simulations can reproduce avascular as well as vascular tumour growth. We thus obtained round tumour until its diameter reaches two millimeters. Larger tumours are progressively deformed according to the nutrient gradient in the tissue: quiescent and necrotic zones are thus obtained as a function of tumour radius and micro-environment. Shaping our grid for reproducing lung anatomic, we were able to reproduce tumour growth constrained by the presence of anatomical structures such as bronchi.

Conclusion:

The structure of the so-obtained tumour is equivalent to those observed in patient using diagnosis imaging; our spatio-temporal model for tumour growth thus provides tumour growth in agreement with clinical and radiological observations.

Citation Format: Louise Viger, Clément Draghi, Fabrice Denis, Christophe Letellier. Modeling spatial tumor growth as seen in clinical and radiological observations. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3760. doi:10.1158/1538-7445.AM2015-3760
Abstract 377: EpCAM+ and EpCAM- circulating tumor cells in metastatic lung cancer
Authors: de Wit Sanne , van Dalum Guus , Lenferink Aufried T.M. , Tibbe Arjan G.J. , Hiltermann Jeroen T.N. , Groen Harry J.M. , van Rijn Cees , Terstappen Leon W.M.M.
Published: August 2015

Purpose: The presence of Circulating Tumor Cells (CTC) in metastatic carcinomas detected by CellSearch is associated with poor outcome. CellSearch uses an enrichment step based on the EpCAM antibody and enumerates CTC using antibodies targeting specific cytokeratins. Here we investigate the presence and role of CTC not detected by CellSearch in lung cancer patients.

Methods: Blood discarded by CellSearch after EpCAM based enrichment was collected and enriched for CTC by filtration through microsieves and enumerated after fluorescent labeling. Additional anti-cytokeratin antibodies were added to the CellSearch test to increase the cytokeratin coverage. This approach was validated using different cell lines spiked into blood and tested on blood samples of 28 metastatic lung cancer patients.

Results: The majority of spiked EpCAM+ cells could be detected with CellSearch whereas few cells were detected with low or no EpCAM expression (EpCAM-). Recovery of cells on microsieves depended strongly on cell size. One or more CTC were detected in 39% of the patient samples, this increased to 75% when adding the CTC detected in the discarded blood and to 82% with the use of additional cytokeratin antibodies. Presence of CTC was significantly associated with poor Overall Survival (OS) when detected by CellSearch without (p = 0.004) and with additional cytokeratins (p = 0.007), but not with EpCAM-CTC in the blood discarded by CellSearch (p = 0.271) or all CTC detected (p = 0.354)

Conclusions: Expanding the cytokeratin coverage and including EpCAM-CTC, double the number of patients with CTC and the number of CTC detected with CellSearch. In contrast with EpCAM+ CTC, the presence of EpCAM-CTC in this group of patients was not associated with poor OS. The metastatic lung cancer patients included in this study were very diverse with respect to cancer type, line of therapy and quite small in numbers to make any definitive conclusions. Still, this pilot study warrants a larger study to confirm the findings. In addition an in-depth characterization of the EpCAM+ and EpCAM-CTC is needed to confirm that the EpCAM-, panCK+ CTC are indeed tumor cells and unravel the genetic difference with the EpCAM+, panCK+ CTC.

Citation Format: Sanne de Wit, Guus van Dalum, Aufried T.M. Lenferink, Arjan G.J. Tibbe, Jeroen T.N. Hiltermann, Harry J.M. Groen, Cees van Rijn, Leon W.M.M. Terstappen. EpCAM+ and EpCAM- circulating tumor cells in metastatic lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 377. doi:10.1158/1538-7445.AM2015-377
Abstract 3771: Tank-binding kinase 1 associates with centrosomes and regulates microtubule dynamics and mitosis
Authors: Pillai Smitha R. , Nguyen Jonathan , Johnson Joseph , Haura Eric , Coppola Domenico , Chellappan Srikumar
Published: August 2015

TANK Binding Kinase 1 (TBK1) regulates interferon signaling and NFκB function by acting as a non-canonical IκB kinase. TBK1 also participates in RalB-mediated inflammatory responses and contributes to the survival of non-small cell lung cancers (NSCLC) driven by oncogenic KRAS. In addition, TBK1 could phosphorylate and activate Akt, modulate autophagy and alter the autocrine cytokine network in cancer cells indicating oncogenic roles in addition to its immune regulatory functions. Our studies reveal that TBK1 plays a novel and direct role in promoting mitotic progression of lung cancer cells by phosphorylating multiple substrates during mitosis as well as by modulating microtubule dynamics. Levels of active phospho-TBK1 are elevated in mitotic cells where it localized to centrosomes, mitotic spindles and midbody as seen by confocal microscopy. Inhibition of TBK1 by kinase inhibitors such as BX795, Amlexanox, MRT67037 or depletion of TBK1 by shRNA resulted in mitotic defects and decreased the number of mitotic cells. TBK1 could interact with the centrosomal protein CEP170 and the nuclear mitotic apparatus protein NuMA as seen by GST binding assays, immunoprecipitation-western blot assays and proximity ligation assays. In addition, TBK1 could phosphorylate CEP170 and NuMA in in vitro kinase assays; mass spectrometry analysis revealed that TBK1 phosphorylated 12 serine residues and a threonine residue of CEP170 and five serine residues of NuMA. Inhibition or depletion of TBK1 prevented the centrosomal localization of CEP170 and the association of NuMA with the spindle poles. TBK1 depletion in A549 and H1650 cells resulted in more stable microtubules; further, depletion of TBK1 inhibited the interaction of CEP170 with the microtubule depolymerase Kif2b and the binding of NuMA to Dynein, resulting in mitotic abnormalities or mitotic arrest. In addition, inhibition of specific interaction between TBK1 and CEP170 using a 13 amino acid peptide resulted in inhibition of mitosis, enhanced microtubule stability and mitotic defects. These results are paradigm shifting that suggest TBK1 plays a significant role in regulating microtubule dynamics and mitotic progression of cells and this might have significant relevance to cancer as well as innate immune response.

Citation Format: Smitha R. Pillai, Jonathan Nguyen, Joseph Johnson, Eric Haura, Domenico Coppola, Srikumar Chellappan. Tank-binding kinase 1 associates with centrosomes and regulates microtubule dynamics and mitosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3771. doi:10.1158/1538-7445.AM2015-3771
Abstract 3773: Plk1-mediated stabilization of 53BP1 suppresses centrosome abnormal amplification
Authors: Yim Hyungshin , Woo Sang-Uk , Shin Sol-Bi , Erikson Raymond L.
Published: August 2015

Mammalian Plk1 has been studied as an essential factor in regulating mitotic events through the phosphorylation of several Plk1-specific substrates. Here we show that in mitosis 53BP1 binds to the C-terminal polo-box domain of Plk1 and is a substrate for Plk1 in vitro. 53BP1 is hyper-phosphorylated and its level is up-regulated in cells expressing wild type Plk1 (Plk1-WT), but not in cells expressing a kinase-defective mutant (Plk1-KM). Depletion of Plk1 reduces the level of 53BP1 which is restored in cells treated with MG132. In cells expressing Plk1-KM but not in Plk1-WT cells, 53BP1 interacts with Mdm2 suggesting that 53BP1 turnover is regulated by Plk1-mediated phosphorylation. In mitosis, 53BP1 colocalizes with Plk1 to the centrosome and the spindle pole. Down-regulation of 53BP1 by shRNA induces multiple centrioles, multiple spindle poles, and mis-orientation of poles in HeLa cells. The data suggest that the phosphorylation of 53BP1 by Plk1 regulates its stability, and that this biochemical event plays a crucial role in modulating chromosomal amplification which ensures bipolarity in mitosis.

Citation Format: Hyungshin Yim, Sang-Uk Woo, Sol-Bi Shin, Raymond L. Erikson. Plk1-mediated stabilization of 53BP1 suppresses centrosome abnormal amplification. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3773. doi:10.1158/1538-7445.AM2015-3773
Abstract 3774: Investigating the role of CDC25B in inhibition of cellular proliferation
Authors: Lee Caleb C. , Manfredi James
Published: August 2015

CDC25B is a dual specificity phosphatase that activates cyclin-dependent kinases to trigger entry into mitosis and is required for re-entry into mitosis after DNA damage. Four isoforms of CDC25B are known to be expressed and some differences in their role in dividing cells versus continuation of the cell cycle after DNA damage have been shown.

As an oncogene, CDC25B is upregulated by c-Myc and activated by Aurora-A. In humans, CDC25B is overexpressed in multiple tumor types and increased levels correlate with worsening tumor grade. In a transgenic mouse model, overexpression of CDC25B in the mammary glands led to accelerated mammary epithelial proliferation resulting in hyperplasia and the formation of tumors when exposed to the carcinogen DMBA. In vitro, co-transfection of CDC25B with Ras allows for transformation of MEF’s.

Surprisingly, given the establishment of CDC25B as an oncogene, colony formation assays using ectopic expression of CDC25B in transformed cell lines reveal an anti-proliferative effect. Although CDC25B has been shown to cause DNA damage and activates p53, our data show that colony formation is decreased independent of p53 status. Preliminary data reveal a role for Ras inhibition as a cause of this anti-proliferative effect. Co-transfection of CDC25B and activated Ras results in decreased expression of the ectopic Ras protein in several cell lines tested. Furthermore overexpression of CDC25B abrogates the G2 arrest and decreases cell viability after pulse treatment with doxorubicin. Taken together, these data suggest a novel mechanism by which CDC25B may inhibit proliferation by decreasing Ras expression.

Citation Format: Caleb C. Lee, James Manfredi. Investigating the role of CDC25B in inhibition of cellular proliferation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3774. doi:10.1158/1538-7445.AM2015-3774