bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABO blood group and the risk of lung cancer: Multicenter, case-control, observational study.
Authors: Utkan Gungor , Urun Yuksel , Cangir Ayten Kayi , Oksuzoglu Omur Berna , Özdemir Nuriye , Oztuna Derya Gokmen , Kocaman Gokhan , Demirkazik Ahmet , Okten Ilker , Icli Fikri 
Published: March 2020

1596 Background: The role of genetic factors in the development of cancer is widely accepted. Previous studies have observed an association between ABO blood group and risk of certain malignancies, including pancreatic and gastric cancer. The data on the role of ABO blood group and Rh factor in lung cancer is limited. Methods: All patients who had Lung cancer (LC) and treated between 2000-2011 at the involved centers with defined ABO/Rh were included in our retrospective reviews of tumor registry records. A group of volunteer healthy blood donors of Turkish Red Crescent between 2004 and 2011 were identified as a control group. The relationship of ABO/Rh with clinical features such as age at diagnosis, histological subtype and sex were evaluated. We compared the distributions of ABO/Rh among 1954 patients and 3,022,883 controls. Among LC patients, differences between each of aforementioned ABO/Rh groups with respect to various clinical features were explored, respectively. Results: Of these patients the median age was 62 (range: 17-90). The 84% of patients were male. Overall distributions of ABO blood groups as well as Rh factor were statistically different between patients (43.6% A, 8.3% AB, 17.3% B, 30.8% O, and 86.3% Rh+) and controls (42.2% A, 7.6% AB, 16.3% B, 33.9% O, and 87.7% Rh+) (p=0,03). In addition, there were statistically significant differences between patients and controls with respect to O vs. nonO (p=0.004) and marginal significance for A vs. nonA (p=0,065), B vs. nonB (p=0,076), and Rh+ vs. Rh- (p=0,057). Among patients, there weren’t statistically significant differences between blood group with respect to sex and age. However there was statistically significant difference between blood group with respect to histology (p=0,001). Although the distribution of A and O were similar according to histology, patients with squamous histology had antigen B more frequently than other histological sub types (p=0,009). Conclusions: In the study populations, ABO blood type was statistically significantly associated with the LC and having blood type other than O increases the risk of LC. Further studies are necessary to define the mechanisms by which ABO blood type may influence breast cancer risk.
Analyzing excess mortality from cancer among individuals with mental illness.
Authors: Musuuza Jackson S. , Sherman Marion E. , Knudsen Kraig J. , Sweeney HelenAnne , Tyler Carl V , Koroukian Siran M. 
Published: March 2020

1598 Background: Previous studies have documented higher cancer-related mortality in individuals with mental illness, compared to their healthier counterparts. The aim of this study was to identify the anatomic cancer sites for which mortality is higher in individuals with mental illness. Methods: We used a linked dataset comprised of death certificate data for the state of Ohio for the years—2004-2007 and data from the publicly funded mental health system in Ohio. Decedents with mental illness were those identified concomitantly in both data sets. We used age-adjusted standardized mortality ratios (SMRs) in race- and sex-specific strata to estimate excess deaths for each of the anatomic cancer sites. Results: Overall, there was excess mortality from cancer associated with having mental illness in Non-Black men and women (SMR: 1.14 (95% confidence interval [CI] = 1.05-1.22), and 1.13 (95% CI= 1.05-1.20, respectively), but lower mortality in Black men, likely due to premature mortality from other causes (0.71 (95% CI= 0.61-0.83). In Black women, we observed no excess mortality from cancer that was associated with having mental illness. There was excess mortality from hepatobiliary cancer in Non-Black men (SMR= 1.65; 95% CI =1.15-2.29), but not in any other sex- and race- stratum. In addition, we observed excess mortality from lung and laryngeal cancers among Non-Black men and women (SMRs for lung cancer of 1.28 (95% CI= 1.13-1.45), and 1.45 (95% CI= 1.29-1.62), respectively; and for laryngeal cancer (2.01 (95% CI= 1.19-3.18 for men, and 2.47 (95% CI= 1.08-4.89) for women). Black women experienced excess mortality from cancer of the kidney and renal pelvis (SMR= 2.91; 95% CI =1.53-5.06), while Non-Black women experienced excess mortality from urinary bladder cancers (SMR=1.89; 95% CI=1.15- 2.92). Conclusions: Compared to the general population in Ohio, individuals with mental illness experienced excess mortality from certain cancers. In part, this excess mortality may be mediated by a higher prevalence of smoking or substance abuse in individuals with mental illness. Further investigation is needed to explain the observed racial variation in cancer mortality, and to examine mortality for specific cancers based on severity of mental illness.
Analysis of KRAS and BRAF mutant colorectal cancers in a multiracial population.
Authors: Acoba Jared David , Lum Christopher A. , Leong Lambert T 
Published: March 2020

1599 Background: We previously demonstrated racial disparities in colorectal cancer (CRC) survival despite adjustments for tumor and socioeconomic factors. Molecular differences in breast and lung tumors contribute to racial survival inequality, yet in CRC, molecular tumor characteristics have not been studied extensively in a racially diverse cohort. We performed a comprehensive evaluation of KRAS and BRAF mutations in a multiracial population to determine the prevalence in CRC and the degree to which these molecular traits impact survival. Methods: A retrospective cohort study of patients diagnosed with CRC between 2008 and 2011 from hospital tumor registries was performed. The prevalence of KRAS and BRAF mutations was determined for the study population and individual racial groups. Multivariable Cox proportional hazards regression models for survival were built for KRAS and BRAF mutation status while adjusting for age at diagnosis, race, and stage of disease. Results: Of 706 patients diagnosed with CRC, KRAS mutational analysis was performed on 148 subjects. 14% of subjects were white (W), 64% Asian (A), and 21% Native Hawaiian/Pacific Islander (NH). KRAS mutation was identified in 48 subjects (32%). The prevalence of mutant tumors among racial groups was W 33%, A 36%, and NH 30%. Analysis for KRAS G13D mutations revealed a prevalence of W 11%, A 9%, and NH 7%. When compared to published datasets of predominantly white patients, our multiracial cohort had a significantly higher rate of KRAS G13D mutant tumors, p=0.039. Of 74 subjects tested for the BRAF mutation, two mutant tumors were detected (3%). The prevalence of the BRAF mutation by race was 10% W, 3% A, and 0% NH (p=0.18). BRAF and KRAS G13D mutations were adverse prognostic factors in a multivariate analysis, although the odds ratios failed to meet statistical significance. Conclusions: The prevalence of BRAF and KRAS mutations in this multiracial cohort is similar to what has been previously reported. However the rates of KRAS G13D and BRAF mutant tumors in our cohort are higher than prior reports. Furthermore, KRAS G13D which has been postulated to be a favorable prognostic factor for CRC, may adversely impact survival of minority patients.
Effect of gender on age-specific effects for ulcerated malignant melanomas.
Authors: Richardson Blakely S. , Anderson William F. , Barnholtz-Sloan Jill , Tucker Margaret A. , Gerstenblith Meg R. 
Published: March 2020

1603 Background: Gender, age at diagnosis, and ulceration are all independent prognostic factors for melanoma. The purpose of this study was to further examine the interactions among gender, age, and melanoma ulceration. Methods: Using the NCI’s SEER 17 Registries Database (2004-2008), we assessed ulceration status among White men and women with malignant melanoma, stratified by younger (ages 10-39 years) and older (ages 40-84 years) ages at diagnosis as well as by tumor depth. The analysis was restricted to melanomas common to both age groups, i.e. superficial spreading, nodular, and unclassified melanomas. There were 2905 older men, 301 younger men, 1624 older women and 276 younger women that fit our criteria. Relative risks were expressed as incidence rate ratios (IRR) with 95% confidence intervals (CI). Results: At every tumor depth, IRRs for ulcerated melanomas were significantly higher for older than younger persons (IRR>1.0). The trend, however, was different in men as compared to women. In men, the IRR (older to younger) rose continuously with increasing depth [≤1.0mm: IRR 7.81 (CI 6.18-9.98), 1.01mm-≤2.0mm: IRR 9.71 (CI 7.55-12.68), 2.01mm-≤4.0mm: IRR 11.04 (CI 8.78-14.06); and ≥4.01mm: IRR 12.26 (CI 9.60-15.87)]. On the other hand, in women, IRR (older to younger) was stable for all depths ≤4.0mm then nearly doubled for melanomas ≥4.01mm [≥4.01mm: IRR 8.00 (CI 5.85-11.20)]. The IRR trend analysis was statistically significant for men (p = 0.01) but not for women (p = 0.34). Conclusions: Our study confirms that older age at diagnosis is associated with higher incidence rates of ulcerated malignant melanomas. This large-scale population-based analysis also shows an effect modification by gender and tumor thickness, suggesting different biologic behavior in melanoma in younger and older men and women. Future studies should further investigate tumor biology differences in these populations and the interactions among gender, age at diagnosis, and ulceration in melanoma.
American BRCA outcomes and utilization of testing (ABOUT) study.
Authors: Sutphen Rebecca , Bauer Joseph E. , Virgo Katherine S. , Casares Carolina , Walker Gregg , Schwartz Marc D , Armstrong Joanne , Friedman Sue , Lynch Kristian , Andrews James , Aguado Loi Claudia X , Toscano Michele , Kotchko Nancy , Teten Rachel Threet , Kondoff Matt R , Brand Lana , Molina Ashley 
Published: March 2020

1608 Background: An estimated 100,000 individuals currently undergo genetic testing for hereditary susceptibility to breast and ovarian cancer annually in the U.S., yet little is known about their characteristics, testing experience or outcomes. Research in this high-risk group has been limited to patients recruited at academic medical centers where case ascertainment, health services delivery, decision-making and, quite likely, outcomes are different from those in the community setting where the majority of individuals currently receive healthcare services. Methods: Eligible subjects include 10,000 consecutive individuals requesting BRCA testing through the nation’s third-largest health insurer, Aetna, beginning in December, 2011. De-identified data are analyzed from each test request form submitted by the ordering provider. Each eligible subject is mailed a study packet inviting them to complete a questionnaire (by mail, online or telephone) designed to investigate informational and healthcare services, test results, knowledge, risk perception and medical intentions. Results: Of 442 subjects contacted during the first two weeks of accrual, 143 (32%) have completed the questionnaire to date. Similar to Aetna member demographics, 7% are African-American and 7% report Hispanic ethnicity. Based on Chi-Square tests, there were no differences between respondents and non-respondents with regard to age (51% under age 50), race, ethnicity or personal history of cancer (58%). Among respondents, deleterious mutations were identified in 8%. Testing for a known familial mutation was performed in 8%. Among women with breast cancer, 13% were undergoing testing prior to initial surgical treatment. Updated results from 3000 eligible subjects will be presented. Conclusions: This innovative, academic-industry collaboration enables an unprecedented investigation of significant issues surrounding individuals at increased risk for hereditary breast and ovarian cancer and undergoing genetic testing in the U.S. The results will guide the development and dissemination of more targeted decision-support tools and strategies to improve medical outcomes for such individuals.
Association between age, gender, residential region, and prevalence of subependymal giant cell astrocytoma among patients with tuberous sclerosis complex: A U.S. Healthcare Claims Database study.
Authors: Kohrman Michael , Sun Peter , Liu Zhimei , Kruger Darcy 
Published: March 2020

1609 Background: Subependymal giant-cell astrocytomas (SEGA) are slow growing non-cancerous tumors that can occur in patients with tuberous sclerosis complex (TSC). The objectives of this study were to examine SEGA prevalence among TSC patients in a real world setting, and to ascertain the relationships between SEGA prevalence and age groups, genders, or residential regions. Methods: We conducted a retrospective cohort study based on a large US commercial healthcare claims database. Patients with a TSC claim between 2000 and 2009 and with 12-month continuous enrollment after their first TSC claim were included into the study. SEGA was identified based on ICD-9CM codes in inpatient or outpatient claims. Patients’ genders, residential regions and ages of their first TSC claim and /or their first SEGA claim (if they had SEGA) were extracted from enrollment files respectively. SEGA prevalence was assessed with subgroup analyses of genders, age groups of first TSC claim, and residential regions. Two-sample t tests and Chi-square tests were used to explore the relationships between SEGA prevalence and age groups, genders, or residential regions. Results: The study had 2,767 patients with a mean age of 28.5 years on their first observed TSC claim, and 55.3% were female. Among these TSC patients, 7.7% had SEGA with variations by age groups of their first TSC claim (5.9% for age<1 year, 12.6% for age 1-5 years, 11.0% for age 6-10 years, 11.0% for age 11-18 years, 7.6% for age 19-25 years, and 5.1% for age 26 years or more), by genders (8.7% for males vs. 6.9% for females), and by residential regions (6.0%-11.0%). The associations between SEGA prevalence and age groups, genders or residential regions were all statistically significant with p<0.05. Conclusions: In a real world setting, and by the end of the first post-TSC year, 7.7% TSC patients had an observed SEGA diagnosis. This prevalence varied by age groups, genders, residential regions. Further research is needed to explore the factors that results into these variations.
Relationship between overall survival and progression-free survival for recent NCCTG glioblastoma multiforme trials.
Authors: Wu Wenting , Galanis Evanthia , Buckner Jan C. , Jaeckle Kurt A. , Sargent Daniel J. 
Published: March 2020

2004 Background: With the approval of novel agents for glioblastoma (GBM) treatment, reliable historical outcome data for the common phase II endpoint of progression free survival (PFS) is not available. In particular, the association between progression and overall survival (OS) has not been evaluated after temozolomide (TMZ) became the standard therapy for newly diagnosed GBM. Methods: Datasets from 5 TMZ-including NCCTG clinical trials in newly diagnosed GBM (n=325, 2005-2011, 1 phase I only and 4 phase I and single arm phase II trials) were pooled and analyzed to evaluate the individual level correlation between PFS and OS using correlation coefficient, landmark analyses, and time-dependent variable analyses. A historical control group was constructed by pooling datasets from 12 pre-TMZ era NCCTG clinical trials in the same patient population (n=1359, 1980-2004). Each of the 5 newer trials was compared to the control group to estimate the treatment effect (hazard ratio) on PFS and OS, which were analyzed to evaluate the trial level correlation between PFS and OS using correlation coefficient and weighted linear regression. Results: The estimated correlation coefficient between PFS and OS at individual patient level is 0.75 (95%CI, 0.7 to 0.8). The estimated hazard ratios of death in the landmark analysis at 4 and 6 months are 2.15 (95%CI, 1.47 to 3.15) and 2.17 (95%CI, 1.57 to 3.12), respectively, and the estimated hazard ratio of death is 10.1 (95%CI, 6.6 to 15.4) when progression is treated as a time-dependent variable. For trial level correlation (against the historical control group), the estimated correlation coefficient between HRos and HRpfs is 0.51 (95%CI, -0.67 to 0.96), with moderate prediction: the predicted HRos is very close to the observed HRos in 4 of 5 cases, however the predicted HRos is significantly different from 1 in only 2 out of 5 cases due to small sample size in other 3 cases. Conclusions: PFS and OS are highly associated at the individual patient level but only moderately at the trial level, the latter possibly due to small sample size in some of the trials. Additional validation in other trials could support use of PFS as a primary endpoint for randomized phase II trials in GBM.
Bayesian adaptive randomized trial design for patients with recurrent glioblastoma.
Authors: Alexander Brian Michael , Wen Patrick Y. , Lee Eudocia Quant , Batchelor Tracy , Cloughesy Timothy Francis , Parmigiani Giovanni , Trippa Lorenzo 
Published: March 2020

2005 Background: Bayesian-based trial design has the ability to utilize accumulating data in real time to alter the course of the trial, thereby enabling dynamic allocation to experimental arms and earlier dropping of ineffective arms. This flexibility results in a potentially more efficient trial framework by increasing the probability of enrollment to arms that show evidence of efficacy. In this study we considered a hypothetical scenario in which patients who have been previously treated on several separate experimental protocols at the Dana-Farber/Harvard Cancer Center and the University of California, Los Angeles were instead enrolled in a single multi-arm protocol utilizing a Bayesian adaptively randomized trial design. The purpose was to determine whether similar scientific results could have been accomplished more efficiently. Methods: We generated an adaptive randomization procedure that was retrospectively applied to primary patient data from four separate phase II clinical trials in patients with recurrent glioblastoma. We then compared AR to more conventional trial designs using realistic hypothetical scenarios consistent with survival data reported in the literature. Our primary endpoint is the number of patients needed to achieve a desired statistical power. Results: If our phase II trials had been a single multi-arm AR trial, bevacizumab would have been identified as an efficacious therapy, and 30 fewer patients would have been needed compared to a multi-arm balanced randomized (BR) design. More generally, Bayesian AR trial design for patients with glioblastoma would result in trials with fewer overall patients with no loss in statistical power, and in more patients randomized to effective treatment arms. For a trial with a control arm, two ineffective arms and one effective arm with hazard ratio 0.6, a median of 47 patients would be randomized to the effective arm compared with 35 in a BR design. Conclusions: Given the desire for control arms in phase II trials, an increasing number of experimental therapeutics for patients with glioblastoma, and a relatively short time for events, Bayesian adaptive designs are attractive for clinical trials in glioblastoma.
Effects of cediranib, a VEGF signaling inhibitor, in combination with chemoradiation on tumor blood flow and survival in newly diagnosed glioblastoma.
Authors: Gerstner Elizabeth Robins , Emblem Kyrre E. , Chi Andrew S. , Eichler April F. , Hochberg Fred , Drappatz Jan , Quant Eudocia Carmen , Norden Andrew David , Pinho Marco C , Polaskova Pavlina , Jennings Dominique , Ancukiewicz Marek , Ivy S. Percy , Wen Patrick Y. , Jain Rakesh K. , Sorensen A. Gregory , Batchelor Tracy 
Published: March 2020

2009 Background: Anti-angiogenic therapy is hypothesized to synergize with radiation and chemotherapy by improving tumor blood flow. We evaluated the tolerability, efficacy and potential mechanism of action of radiation, temozolomide, and cediranib in newly diagnosed glioblastoma patients. Methods: Newly diagnosed glioblastoma patients were treated with radiation, temozolomide, and cediranib followed by monthly temozolomide for 6 cycles and daily cediranib until tumor progression or toxicity as part of an IRB-approved, Phase Ib/II clinical trial. MRI scans including measurement of cerebral blood flow were performed at baseline, weekly during the 6 weeks of chemoradiation and then monthly. Radiographic response was determined by RANO criteria. Results: Six patients were enrolled in the phase Ib part of the study with cediranib 30 mg daily in combination with temozolomide and radiation. No dose-limiting toxicities were identified. Forty patients were enrolled in the phase II part of the study. Among the entire cohort of 46 patients, median age was 57 (range 35-74), median KPS was 90% (60-100), 36 patients underwent a subtotal resection and 10 underwent biopsy. 26/30 patients taking corticosteroids were able to taper corticosteroids during chemoradiation. Off study reasons included toxicity (14), disease progression (18), and patient preference (2). Five patients remain on study without disease progression and 20 patients have died. Median duration on study was 158 days. Median progression free survival was 288 days (95%CI 240,∞) and median overall survival was 786 days (95%CI 411 ,∞). Best radiographic response in patients who completed chemoradiation was CR in 2 patients, PR in 20 patients, and SD in 15 patients. Patients with increased tumor perfusion during chemoradiation survived nearly 1 year longer (mean OS=611 days) than patients with decreased perfusion (mean OS=269 days). Conclusions: Cediranib was well tolerated and led to improved PFS and OS compared to historical controls, particularly in those with improved perfusion. This combination is being evaluated in an ongoing randomized trial (RTOG 0837).