bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mediation of black/white disparities in triple negative breast cancer by socioeconomic position, reproductive factors and diabetes in the Nurses’ Health Study Cohorts I & II.
Authors: Marcus Lydia , Dookeran Keith A. 
Published: May 2020

1565 Background: The higher rates of triple negative (TN) breast cancer (BC) observed among black compared to white women may be attributable to social and reproductive factors, as well as biological conditions like diabetes mellitus type 2. We examine the extent to which the black/white race disparity in TNBC is transmitted through these factors. Methods: Data are from the Nurses’ Health Study I and II prospective cohorts and include non-Hispanic (nH) black (n = 97) and nH white (n = 8,876) women aged 25-55 years at enrollment with invasive BC diagnoses. Participant characteristics are self-reported or drawn from medical records. We estimated average controlled direct associations (ACDA) using logistic regression with model-based standardization to evaluate the age/body mass index (BMI)-adjusted prevalence difference for TN versus luminal A/B type BC by race, and performed a series of ACDA (with comparison of rescaled coefficients (RC)) controlling for diabetes, mean family income before diagnosis (cont.), husband’s education ( < college, college, graduate school), parental ownership of participant’s childhood home (yes/no), age at menarche (cont.), age at first birth (cont.), parity (integer), and breastfeeding (BF) (parous/never BF, parous/ever BF). Results: Compared to nH whites, nh black women had higher prevalence of TNBC (24.5% v. 45.4%; p < 0.01), higher prevalence of diabetes (5.5% v. 11.3%; p = 0.01), lower prevalence of BF (59.2% v. 46.6%; p = 0.02), higher mean BMI (26.1 v. 29.9; p < 0.01), and lower mean family income ($17,304 v. 15,750; p < 0.01). BMI, age, and menopause were positively associated with prevalence of diabetes. In the age/BMI adjusted model, nH black women were 20%-points more likely than nH whites to have TNBC (95% Confidence Interval (CI): 0.11, 0.29). This disparity was reduced to 18.1% after also adjusting for BF (95% CI: 0.09, 0.28), to 13.7% after additionally adjusting for socioeconomic indicators (95% CI: 0.02, 0.25), and to 13.3% after adjusting for all potential mediators (95% CI: 0.01, 0.26). Based on the method of RC, socioeconomic indicators accounted for the largest fraction of mediated effects and BF accounted for most of main effect attenuation associated with reproductive factors; diabetes accounted for negligible effect. Conclusions: Our findings support the hypothesis that observed racial differences in TNBC diagnoses may be at least partially mediated by differences in socioeconomic position and reproductive patterns, namely breastfeeding.
Malignancies associated with DPP4 inhibitors and GLP1 receptor agonists: Data from a large real-world database.
Authors: Wang Jiasheng , Kim Chang H. 
Published: May 2020

1567 Background: DPP44 inhibitors (DPP4i) and GLP1 receptor agonists (GLP1Ra) control type 2 diabetes (T2DM) by promoting GLP-1 pathway; its activation can lead to dysplasia or tumor inhibition based on tissue types. Moreover, DPP4 can act as a tumor suppressor or activator. Few studies have looked at the risk of DPP4i and GLP1Ra on various types of cancer. Methods: We inquired an aggregated electronic health record database, Explorys (IBM, NY). Patients (Pts) diagnosed with T2DM from 1/05 to 6/19 were included and followed for 5 years after starting DPP4i, GLP1Ra, or metformin. Odds ratio (OR) were calculated after 6mo of lag time. Results: We identified 344,550, 112,000, and 1,245,930 pts in the DPP4i, GLP1Ra, and metformin group, respectively. The three groups were well balanced except pts in the GLP1Ra group had higher BMI. Within 5 years, 24,260 pts (9.5%) in DPP4i, 5,580 (8.7%) in GLP1Ra, and 57,490 (9.3%) in metformin group developed any types of cancer. When adjusted for sex, age, smoking status, alcohol abuse history, hemoglobin A1C (≤9.0% vs > 9.0%) and BMI ( < 30 vs ≥30 kg/m2) around initiation of antidiabetic agents, the aOR was 1.01 (95%CI .94-1.08) for DPP4i and 1.06 (95%CI .93-1.20) for GLP1Ra, comparing with the metformin group. For specific cancer types, DPP4i users were associated with significantly higher risk of bladder, kidney, liver cancer and melanoma; while the risk of breast, lung and prostate cancer were reduced. GLP1Ra users were associated with higher risk of thyroid cancer; while the risk of bladder, colon, lung, and prostate cancer were reduced. Conclusions: DPP4i and GLP1Ra were not associated with increased cancer risk overall. However, they were associated with increased or decreased risk of specific cancer types. [Table: see text]
Metabolic syndrome, metabolic comorbid conditions, and risk of early-onset colorectal cancer.
Authors: Chen Hanyu , Li Zitong , Zheng Xiaobin , Hur Jinhee , Zong Xiaoyu , Chapman William , Nickel Katelin B. , Tipping Andrew , Colditz Graham A. , Olsen Margaret A. , Giovannucci Edward L. , Fields Ryan , Cao Yin 
Published: May 2020

1571 Background: The etiology and contributors to the rising incidence of early-onset colorectal cancer (CRC diagnosed under age 50), driven largely by distal and rectal cancer, remain largely unknown. Metabolic syndrome is associated with higher risk of CRC diagnosed at older ages; however, its association with early-onset CRC remains unclear. Methods: We conducted a nested case-control study among participants aged 18-50 years with ≥2 years of enrollment and prescription drug coverage in the IBM MarketScan Commercial Databases (2006-2015). Incident CRC cases were identified using ICD-9-CM diagnosis codes. Controls without any cancer were identified using frequency matching on age, sex, geographical region, and duration of insurance enrollment. Metabolic syndrome was defined using either ICD-9-CM diagnosis codes or the presence of at least 3 of the following: obesity, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes. In addition to ICD-9-CM codes, hypertension, hyperlipidemia, and hyperglycemia/type 2 diabetes were also defined based on regular use of medications. Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 4,673 early-onset CRC and 40,832 controls were included. Metabolic syndrome was associated with increased risk of early-onset CRC (OR: 1.33, 95% CI 1.16-1.52), after adjusting for a range of potential confounders. The number of metabolic comorbid conditions was positively associated with risk of early-onset CRC in a dose-response fashion. Compared to individuals without any conditions, individuals with 1, 2, ≥3 metabolic conditions had a 13% (OR: 1.13, CI 1.04-1.22), 18% (OR: 1.18, CI 1.07-1.31), and 40% (OR: 1.40, CI 1.22-1.61) higher risk of early-onset CRC (Ptrend<0.001), respectively. These associations were driven by proximal (OR for ≥2 vs 0 metabolic comorbid conditions: 1.40, CI 1.15-1.69) and distal colon cancer, OR ≥2 vs 0: 1.25, CI 1.03-1.53), but not rectal cancer (OR≥2 vs 0: 1.07, CI 0.92-1.24). Conclusions: Metabolic syndrome and metabolic comorbid conditions were associated with increased risk of early-onset CRC, largely driven by proximal and distal colon cancer. Metabolic dysregulations may contribute to the rising incidence of early-onset CRC.
Geographic disparity of outcome in patients with cancer over decades: The surveillance, epidemiology, and end results.
Authors: Sakurai Kenichi , Kantarjian Hagop M. , Sasaki Koji , Jabbour Elias , Ravandi Farhad , Konopleva Marina , Borthakur Gautam , Wierda William G. , Daver Naval Guastad , Takahashi Koichi , Naqvi Kiran , Dinardo Courtney Denton , Bravo Guillermo Montalban , Issa Ghayas C. , Jain Preetesh , Pierce Sherry A. , Soltysiak Kelly A , Garcia-Manero Guillermo , Tingen Martha S , Cortes Jorge E. 
Published: May 2020

1574 Background: Improvements in prevention, early detection and therapy of cancer have decreased cancer related mortality yet health disparities continue to exist. We investigated the impact of such disparities in cancer survival. Methods: In the Surveillance, Epidemiology, and End Results, we identified 784,341 patients with cancer from 1990 to 2016 in Georgia; 68,493 in 1990-1999, 371,353 in 2000-2009, and 322,932 in 2010-2016. We assessed overall survival (OS) of patients with all cancers, chronic myeloid leukemia (CML), and lung cancer given the dramatic improvement in patient outcomes in CML since 2000 compared to the consistently poor outcome in lung cancer. We assessed distance from each county to the one National Cancer Institute-designated cancer center (NCI-CC) in Georgia. Results: The 5-year OS of patients with any cancer was 55% with median OS 80 months; the 5-y OS of each county ranged from 33% to 82% (interquartile range[IQR], 51%-65%)(P < 0.001). The improvement of OS was minimal over decades: 5-year OS was 52%, 55%, and 55% in 1990-1999, 2000-2009, and 2010-2016, respectively; the median was 69 months, 80 months, not reached, respectively (P < 0.001). In patients with lung cancer and CML, the 5-year OS was 15% and 52% with the median of 9 months and 67 months, respectively. The geographic difference between counties was relatively small and constant over time in patients with lung cancer, represented by the width in the range and IQR: range 5%-17%, IQR 9%-13%, median 13% in 1990-1999; range 2%-24%, IQR 10%-14%, median 14% in 2000-2009; and range 4%-24%, IQR 12%-17%, median 17% in 2010-2016. However, the geographic difference was more prominent in patients with CML and widened after introduction of modern therapy: range 20%-42%, IQR 26%-34%, median 32% in 1990-1999; range 14%-83%, IQR 38%-64%, median 53% in 2000-2009; and range 14%-80%, IQR 40%-57%, median 57% in 2010-2016. Multivariate Cox regression showed age (hazard ratio[HR],1.040;95% confidence interval[CI],1.039-1.040;P < 0.001), median county income (HR,0.919;95% CI,0.916-0.921;P < 0.001), African American (HR,1.021;95% CI,1.210-1.227;P < 0.001), and distance to NCI-CC (each 100 kilometers) (HR,1.021;95% CI,1.017-1.025;P < 0.001) as predictive factors. Conclusions: The disparity of cancer care exists between geographic locations. The geographic difference of survival seems more prominent when highly effective therapies are available.
Effect of genetic testing results on patient-reported quality of life among patients undergoing panel testing for newly diagnosed ovarian cancer.
Authors: Lee Sarah S. , Frey Melissa Kristen , Gerber Deanna , Schwartz Zachary Phillip , Martineau Jessica , Lutz Kathleen , Reese Erin , Dalton Emily , Olsen Anne , Girdler Julia , Pothuri Bhavana , Boyd Leslie R. , Curtin John Patrick , Levine Douglas A. , Blank Stephanie V. 
Published: May 2020

1584 Background: This study compared patient-reported stress, anxiety, and depression between newly diagnosed ovarian cancer patients with pathogenic genetic testing results versus patients with non-informative results (i.e., variants of uncertain significance (VUS) or negative). Methods: Patients underwent genetic testing (GT) via a facilitated referral pathway (Frey et al, Gynecol Oncol 2020) through which they were referred for genetic counseling and GT by their gynecologic oncologist within six weeks of diagnosis from 10/2015 to 5/2019. English-speaking patients completed three quality of life (QoL) instruments: Impact of Events Scale (IOES), State-Trait Anxiety Questionnaire (STAI), Hospital Anxiety and Depression Scale (HADS) immediately pre-and post-GT and 6 months post GT. Two-way mixed ANOVA was performed to analyze effect of GT results on QoL over time with significance p < 0.05. Results: One hundred ten patients were enrolled in the pathway and 83 (76%) patients underwent GT. Among these, 15 (18%) had potentially actionable pathogenic mutations ( BRCA1-8, BRCA2-4, MSH2-2, MRE11A-1); 26 (31%) had VUS results; 3 (4%) had both a pathogenic mutation and a VUS result; and 42 (51%) had negative results. Sixty patients (72%) completed QoL assessments pre and post GT, and 37 (44%) patients at 6-9 months post GT. For all patients, GT results did not affect QoL scales across our time points. By mean scores across all-comers, patients demonstrated mild stress at each time point and clinically significant anxiety immediate post-GT. All patients had a statistically significance decrease in HADS depression scores over time from pre-GT to 6 months post-GT (mean score 4.98 vs 2.97, p = 0.020). Patients with VUS had lower HADS mean anxiety scores across time (3.62) compared to patients with pathogenic (7.44) or negative mutations (6.83, p = 0.029). For patients without mutations, there was a significant decrease in clinically significant anxiety by STAI-state score at 6 months (p = 0.002) and a decrease in borderline anxiety by HADS scores at 6 months (p = 0.005). This effect was not present for patients with pathogenic mutations or VUS. Conclusions: A pathogenic result does not impact QoL scales immediately pre or post GT or at 6 months post GT, though patients with negative mutations were more likely to show a decrease in anxiety over time. Patients should be recommended GT at time of diagnosis of ovarian cancer without concern of increased stress, anxiety, or depression based on GT results.
Streamlining the genetics pipeline to increase testing for patients at risk for hereditary prostate cancer.
Authors: Tong Barry , Borno Hala , Small Eric Jay , Alagala Fern , Blanco Amie , Dhawan Mallika Sachdev 
Published: May 2020

1590 Background: Metastatic prostate Cancer (mPCa) is increasingly recognized as a heritable disease and germline genetic testing has increasingly become a part of standard of care. At the University of California at San Francisco (UCSF) Genitourinary (GU) Medical Oncology clinic, approximately 850 new patients with mPCa are seen annually. A feasibility pilot Genetic Testing Station (GTS) was developed to expand access to genetic testing among this high-risk population. GTS is facilitated by Genetic Counselor Assistants (GCA) under the supervision of genetic counselors. Methods: This is a feasibility pilot of a GTS model among patients with mPCa. In this model, all patients with mPCa are offered a same day GTS visit with a GCA. At the GTS, the patient receives pre-test education via videos developed by genetic counselors. The patient provides informed consent, a family history, and a saliva sample for Invitae’s 87-gene panel. All positive results trigger a genetic counselor visit while non-positive results either receive a letter or a genetic counselor visit (in person or via telehealth). To evaluate the model, testing frequency and laboratory turnaround time (TAT) was assessed before and after the pilot. Results: In the first four months of the GTS pilot (10/14/2019 – 02/10/2020), 94 patients were referred and received genetic testing. Eight germline positives were identified (BRCA2, CHEK2, HOXB13 MSH6, RECQL4). The average TAT was 8 days. 9.3% of patients were found to have pathogenic mutations through the prostate GTS which is comparable to previously published rates of germline mutations in metastatic prostate cancer patients. In a 4-month time frame the prior to the intervention (10/01/2018-1/31/2019), 26 genetic testing orders were placed. The average laboratory TAT in this prior process was 17 days. Rates of positive germline mutations in the prior model was 8.6%. Conclusions: The GTS is a feasible method to increase access to germline genetic testing among a high-risk population. It may reduce barriers to testing and facilitate real-time discussion of treatment and prevention strategies with patients and family members. As a result, we will continue to operate the GTS. This model provides a framework for scaling access for and cascade testing in other high-risk patient groups.
Results of a prospective phase II national study: Prophylactic radical fimbriectomy (NCT01608074), in women with a documented high risk of breast/ovarian cancer—Final pathological results and outcomes.
Authors: Leblanc Eric , Narducci Fabrice , Hudry Delphine , Mailliez Audrey , Lemaire Anne-Sophie , Tresch-Bruneel Emmanuelle , Salzet Michel , Pomel Christophe , Caquant Frederic , Houvenaeghel Gilles , Charvolin Jean-Yves , Crouzet Agathe , Guyon Frederic , Fouche Yves , Ferron Gwenael , Gouy Sebastien , Vaini-Cowen Veronique , Fourchotte Virginie , Golfier Francois , Collinet Pierre 
Published: May 2020

1594 Background: Risk-reducing salpingo-oophorectomy (RRSO) is the gold standard in surgical prophylaxis of pelvic high-grade serous carcinoma (HGSC) for women at risk of breast/ovarian cancer. Due to significant adverse effects of early oophorectomy, 20-30% of women delay or deny performing this operation. Recent data highlight the fallopian origin of most pelvic HGSC, especially its fimbrial part. Thus, we suggested a new two-step risk-reducing procedure: the radical fimbriectomy (RF) with delayed oophorectomy (DO) (Leblanc et al Gyn Oncol 2011), leading to the current RF/DO Phase 2 study. We present the definitive results on primary and secondary objectives of this trial. Methods: BRCA1/2 carriers or any women with a documented familial risk of breast/ovarian cancer were first counseled to perform a classical laparoscopic RRSO. If they denied, they were offered to enter the RF/DO study. All specimens were submitted to the SEE-FIM pathological protocol. Pathological data along with all intra- and 30-day and beyond post-operative adverse events were prospectively recorded. Follow-up consisted in an annual clinical breast and gynecological examination, with tumor markers and hormonal status assessment. Primary endpoint was the rate of pelvic serous carcinoma. Secondary endpoints were procedure morbidity, rates of tubal abnormalities, breast cancer, secondary oophorectomy. Results: From January 2012 to October 2014, 121 RF were performed: 120 by laparoscopy, 1 laparotomy (concurrent myomectomy). An occult neoplasia was found in 3 cases with 1 invasive HGSC. Intraoperative complications were two grade1 bleedings without transfusion with no grade ≥3 early post-operative or delayed complication. With a median follow-up of 5.3 years (0.2 -7.6), no patient developed any pelvic HGSC, 21 patients developed a breast cancer (3 de novo, 18 recurrences/contralateral.). 1 cancer-free BRCA1-mutated lady delivered safe twins, after an uneventful post-RF pregnancy obtained with assisted reproductive technology (ART). Overall, 29 women underwent DO (by choice: 12 or menopause: 17) resulting in grade 3b complication in 1 case, but no pathological abnormality. Conclusions: RF/DO appears as a safe, well tolerated and effective procedure in terms of occult neoplasia detection. A successful pregnancy with ART was possible after radical fimbriectomy. Longer follow-up and larger cohort are necessary to confirm its efficacy in terms of ovarian cancer prophylaxis. Clinical trial information: NCT01608074.
Multi-institutional comparative effectiveness of advanced cancer longitudinal imaging response evaluation methods: Current practice versus artificial intelligence-assisted.
Authors: Smith Andrew Dennis , Allen Brian C. , Abou Elkassem Asser , Mresh Rafah , Lirette Seth T. , Shrestha Yujan , Giese J. David , Stevens Reece , Williams Dillon , Farag Ahmed , Khalaf Ahmed ,   Society of Abdominal Radiology Emerging Technology Commission on Artificial Intelligence
Published: May 2020

2010 Background: Current-practice methods to evaluate advanced cancer longitudinal tumor response include manual measurements on digital medical images and dictation of text-based reports that are prone to errors, inefficient, and associated with low inter-observer agreement. The purpose of this study is to compare the effectiveness of advanced cancer longitudinal imaging response evaluation using current practice versus artificial intelligence (AI)-assisted methods. Methods: For this multi-institutional longitudinal retrospective study, body CT images from 120 consecutive patients with multiple serial imaging exams and advanced cancer treated with systemic therapy were independently evaluated by 24 radiologists using current-practice versus AI-assisted methods. For the current practice method, radiologists dictated text-based reports and separately categorized response (CR, PR, SD, and PD). For the AI-assisted method, custom software included AI algorithms for tumor measurement, target and non-target location labelling, and tumor localization at follow up. The AI-assisted software automatically categorized tumor response per RECIST 1.1 calculations and displayed longitudinal data in the form of a graph, table, and key images. All studies were read independently in triplicate for assessment of inter-observer agreement. Comparative effectiveness metrics included: major errors, time of image interpretation, and inter-observer agreement for final response category. Results: Major errors were found in 27.5% (99/360) for current-practice versus 0.3% (1/360) for AI-assisted methods (p < 0.001), corresponding to a 99% reduction in major errors. Average time of interpretation by radiologists was 18.7 min for current-practice versus 9.8 min for AI-assisted method (p < 0.001), with the AI-assisted method being nearly twice as fast. Total inter-observer agreement on final response categorization for radiologists was 52% (62/120) for current-practice versus 75% (90/120) for AI-assisted method (p < 0.001), corresponding to a 45% increase in total inter-observer agreement. Conclusion: In a large multi-institutional study, AI-assisted advanced cancer longitudinal imaging response evaluation significantly reduced major errors, was nearly twice as fast, and increased inter-observer agreement relative to the current-practice method, thereby establishing a new and improved standard of care.