bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does the extent of therapy differ between breast cancers detected by screening mammogram and non-screening methods?
Authors: Den Brok Wendie-Lou D. , Speers Caroline , Gondara Lovedeep , Nichol Alan , Wilson Christine , Lohrisch Caroline A. 
Published: September 2018

1544 Background: There is ongoing debate about the role of screening mammography and its impact on overall survival in breast cancer. We hypothesized that women with screen-detected breast cancers (SDBC) receive less surgery, regional radiotherapy (RRT), and chemotherapy (CH) than women with non-screen-detected breast cancers (NSDBC). Less therapy equates to less personal and societal burden, including less time away from work, fewer side effects, lower health care and disability costs, and reduced psychosocial distress. These may be adequate justification for screening programs even in the absence of an overall survival benefit. Methods: Women aged 40-79 years with stage 0-III breast cancers diagnosed between 2007-2012 and referred to the British Columbia Cancer Agency were identified using the Breast Cancer Outcomes Unit database. Clinical and tumor characteristics and type/extent of treatment were extracted. Linkage with the Screening Mammography Program of British Columbia segregated cases into SDBCs and NSDBCs. Interval breast cancers arising in regularly screened women (minimum 2-year interval) were excluded. Results: We identified 12,393 women; 7807 with SDBC and 4586 with NSDBC. Compared with NSDBCs, SDBCs were lower stage, less often treated with mastectomy and CH, and occurred in slightly older women (Table 1). SDBC received more radiation than NSDBC. Conclusions: Women with NSDBC are more likely to present with higher stage breast cancer. Rates of mastectomy and CH were 20% higher in NSDBC whereas SDBC had a modest 5% higher rate of RRT. These findings suggest that screening mammography decreases the extent of local and systemic treatment for breast cancer. [Table: see text]
Impact of patient-provider race/ethnicity and gender concordance on cancer screening: Findings from medical expenditure panel survey.
Authors: Malhotra Jyoti , Rotter David , Tsui Jennifer , Llanos Adana , Balasubramanian Bijal A , Demissie Kitaw 
Published: September 2018

1547 Background: Racial/ethnic minority groups experience lower rates of cancer screening compared to non-Hispanic (NH) whites. Previous studies evaluating the role of patient-provider race/ethnicity and gender concordance in cancer screening have been inconclusive. Methods: We conducted a cross-sectional study of 18,690 patient-provider pairs using the 2003-2010 Medical Expenditure Panel Survey (MEPS) data. We assessed association between patient-provider race/ethnicity and gender concordance and, screening adherence for breast, cervical, and colorectal cancer using American Cancer Society guidelines. Separate multivariable logistic regression adjusting for demographics, self-reported health and MEPS survey year were conducted to examine relationships of interest. Results: Seventy percent of patients were NH-white, 15% were NH-black and 15% were Hispanic. Patients adherent to cancer screening were more likely to be non-Hispanic, better educated, married, wealthier, and privately insured. Among NH-black and NH-whites, patient-provider racial/ethnic concordance was not associated with screening adherence. Among Hispanics, patient-provider racial/ethnic discordant pairs had higher colorectal cancer screening rates as compared to concordant pairs (OR 1.48; 95% CI 1.28-1.71). This association was significant even on adjusting for gender concordance and survey language (English vs. Spanish). Conversely, patient-provider gender discordance was associated with lower rates of breast (OR 0.81; 95% CI 0.74-0.89), cervical (OR 0.79; 95% CI 0.72-0.87) and colorectal cancer (OR 0.86; 95% CI 0.80-0.93) screening adherence in all patients. This association was also significant on restricting analysis to racial/ethnic concordant pairs. Conclusions: Patient-provider gender concordance positively impacts adherence to cancer screening and this finding may guide future interventions. Patient-provider racial/ethnic concordance is not associated with screening adherence among whites and blacks but Hispanic patients seen by Hispanic providers have lower colorectal cancer screening rates. This counter-intuitive finding requires further study.
Breast cancer screening practices with high-risk women: A cross-sectional survey.
Authors: Blaes Anne Hudson , Vogel Rachel Isaksson , Raymond Nancy , Talley Kristine , Allen Alicia , Nagler Rebekah , Teoh Deanna Gek Koon , Mason Susan , Wyman Jean 
Published: September 2018

1550 Background: Little literature exists on primary care providers’ knowledge and preferences towards breast cancer screening for high-risk women. While guidelines recommend MRI and mammography, it is unclear how frequently these recommendations are used. Methods: This web-based survey of providers licensed to practice in Minnesota was conducted. This analysis focuses on breast cancer screening practices for high-risk women. Data were summarized using descriptive statistics; professional characteristic comparisons were conducted using Chi-squared tests. Results: 805 of 10,392 (8%) invitees completed the survey. 72.2% were female. 43.9% were physicians (20.8% internists, 71.7% family medicine, 6.3% gynecology), 11.4% physician assistants (PAs), 44.8% advanced practice registered nurses (APRNs). 84.8% were in community practice, 38% > 20 years of experience and 27.1% < 10 years. When asked how effective screening was for reducing cancer mortality in high risk women, mammography was thought to be very effective (48.8%) or effective (46.8%) in women ages 40-49 years, for women ages 50+ years, 60.8% and 35.7%, respectively. 62.4% thought breast MRI was very effective in reducing cancer mortality in high risk women. There was no difference in breast MRI recommendation based on professional background, experience or practice setting. Female practitioners, less experience, and those working in gynecology or women’s health were more likely to recommend breast MRI. A case vignette for high risk screening cancer survivors is provided (Table). Conclusions: Most primary care providers believe mammography is helpful in women at high risk for developing breast cancer. Less than half of practitioners, however, are following guideline specific recommendations of both mammography and MRI for breast cancer screening in high-risk patients. [Table: see text]
Health4Families: An intervention to improve weight and health behaviors in families with hereditary breast/ovarian cancer or Lynch syndrome.
Authors: Peterson Susan K. , Strong Larkin , Schembre Susan , Cox Matthew , Li Liang , Karam Courtney , Song Jaejoon , Arun Banu , Pande Mala , You Y. Nancy , Rodriguez-Bigas Miguel A. , Lu Karen H. , Lynch Patrick M. , Basen-Engquist Karen 
Published: September 2018

1555 Background: Physical activity, diet, and healthy weight may reduce cancer risk in hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS) families. Evidence-based programs to help affected families make these behavioral changes are lacking. We evaluated data from a 16-week family-centered lifestyle intervention trial for individuals with HBOC or LS germline gene mutations and their relatives. Methods: Index cases with HBOC- or LS-associated mutations were recruited from an institutional registry and advocacy organizations, and identified relatives to participate with them in the study. Those eligible had BMI>25 and/or did not meet recommendations for exercise or fruit/vegetable consumption. Participants were randomized to multiple conditions including text messaging, online weight/diet monitoring, an online social network, and E-mail or telephone coaching. All monitored activity using Fitbits. Behavioral outcomes were assessed online at baseline and 8 weeks. Results: 65 HBOC index cases with 63 family members, and 35 LS index cases with 36 family members participated in the study. At 8 weeks, participants lost 3.2 pounds on average (p<.0001) and increased weekly physical activity from 126 to 172 minutes (p=.0012). LS participants decreased self-reported sedentary time (p=.0126). Program effects did not differ between index cases and family members. Participants reported high program satisfaction; 78% would recommend it to a family member. Conclusions: Hereditary cancer families can benefit from behavioral interventions to improve weight and physical activity. Data show that distance-based methods are effective, and are ideally suited for families with a hereditary predisposition to cancer but who are often geographically dispersed. Clinical trial information: NCT02194387. [Table: see text]
Effect of metformin chemoprevention on metabolomics profiles in Li-Fraumeni Syndrome (LFS).
Authors: Walcott Farzana L. , Annunziata Christina M. , Sotomayor Eduardo M. , Fojo Antonio Tito 
Published: September 2018

1556 Background: LFS is a highly-penetrant, autosomal dominant, cancer predisposition disorder characterized by early onset cancer; germline mutations in TP53are present in 70% of LFS. We previously observed metformin inhibition on mitochondrial function in LFS patients. Metformin may reduce TCA cycle and glycolytic intermediates during cellular transformation, indicating inhibition of complex I of the mitochondria. To further explore this, we performed untargeted metabolomics profiling on stored serum of study participants. To our knowledge, there are no previous studies of metabolomics profiling in LFS patients treated with metformin. Methods: Adult LFS patients (≥18 years old) were enrolled for 20 weeks. Metformin was initiated at 500 mg per day and increased in 500 mg dose increments every two weeks to a maintenance dose of 2000 mg of metformin. Patients were taken off metformin for the last six weeks of the study (week 20). Global biochemical profiles were determined in human serum samples collected in 21 patients, each providing one sample at baseline, week 14 (on 2000 mg metformin) and week 20 (off metformin). Metabolomics analyses were performed by Metabolon, Inc. Results: Treatment with metformin induced a strong metabolic signature of increased fatty acid beta-oxidation in LFS patients. Acylcarnitines, long chain fatty acids, and 3-hydroxy fatty acids were significantly elevated following metformin treatment. TCA cycle intermediates, aconitate, malate, and fumarate were also increased as were levels of ketone body 3-hydroxybutyrate (BHBA)indicating robust β-oxidation, presumably to support increased energy production via the TCA cycle. Clearance of metformin results in normalization of levels to comparable baseline values, indicating a causal role of metformin in these changes. Conclusions: Global metabolomics profiling suggests an increase in TCA cycle intermediates and a strong signature of fatty acid oxidation with metformin treatment in LFS, suggesting metformin effect on the mitochondria and TCA cycle is more dynamic than previously shown. LFS patients may have distinct metabolic profiles which may be altered by treatment with metformin. Funding: ASCO Young Investigator’s Award 2016. Clinical trial information: NCT01981525.
Assessment of BRCA testing uptake in ovarian cancer patients during the implementation of an oncologist-led genetic counseling model at an urban and suburban teaching hospital.
Authors: Jorgensen Jennifer , Chiu Kimberley , Gotimer Kristin , Chalas Eva , Kuo Dennis Yi-Shin , Huang Gloria S. 
Published: September 2018

1589 Background: BRCA testing has become an integral component of ovarian cancer management; however, low testing uptake remains an obstacle. This study evaluated the impact of an oncologist-led counseling and testing model on BRCA testing uptake. Methods: The ENGAGE study (NCT02406235) is a prospective study of an oncologist-led BRCA counseling and testing model in patients with epithelial ovarian, primary peritoneal and fallopian tube cancer (EOC). The United States lead accruing gynecologic oncology sites were Montefiore, an urban academic medical center; and Winthrop, a suburban teaching hospital. Oncologists were trained in BRCA counseling prior to site activation, and directly submitted patients’ samples for BRCA testing. Prior to the ENGAGE study, EOC patients were referred to genetics professionals for counseling and testing. We determined the number of BRCA tests performed, and simple descriptive statistics were used to summarize the data. Results: A combined total of 141 EOC patients underwent BRCA testing during the 20 consecutive months analyzed. In the 10 months pre-ENGAGE, 8 Montefiore patients had BRCA testing, all submitted through the genetics division. Nineteen Winthrop patients had BRCA testing, 16 from their oncologist’s office and 3 from an external genetics office. During the 10-month ENGAGE trial, 64 Montefiore patients and 50 Winthrop patients had BRCA testing. This represents a four-fold increase in BRCA testing uptake, with 114 patients tested during ENGAGE versus 27 patients tested pre-ENGAGE. Of these 114, 99 had BRCA counseling and testing through their oncologist’s office. Conclusions: Implementation of an oncologist-led genetic counseling and testing model was associated with increased BRCA testing among ovarian cancer patients in both the urban and suburban hospitals. Increased BRCA testing could be related to increased patient convenience and standardized training of the clinical team. These findings may guide other institutions as they implement streamlined genetic counseling and testing protocols.
Multicenter study to demonstrate radiomic texture features derived from MR perfusion images of pseudoprogression compared to true progression in glioblastoma patients.
Authors: Elshafeey Nabil , Kotrotsou Aikaterini , Giniebra Camejo Dunia , Abrol Srishti , Hassan Islam , El Salek Kamel , Hassan Ahmed , Shaaban Ahmed , Bergamaschi Samuel , Moron Fanny E , Law Meng , Zinn Pascal , Colen Rivka R. 
Published: September 2018

2016 Background: To differentiate between pseudoprogression and true progression in patients with glioblastoma using MR perfusion radiomic texture analysis (TA). Methods: 98 patients with pathologically-proven diagnosis of GBM were retrospectively included in this IRB approved HIPAA compliant study. All patients underwent DSC and DCE Perfusion MRI as part of their routine clinical care. Images were analyzed using Nordic ICE 2.3 (NordicNeuroLab) ; rCBV and ktrans maps were obtained. Subsequently, 3D slicer 4.3.1(http://www.slicer.org) was used to segment the entire tumor on the different processed maps to create a volume of interest (VOI) for Radiomic TA. Multiple invariant texture features where then extracted from each VOI. 475 invariant texture features were applied to each map. Leave-one-out cross-validation (LOOCV), receiver operating characteristic (ROC), Kaplan Meier, and multivariate Cox proportional hazards regression analyses were used to assess the relationship between texture feature and pseudoprogression and true progression. Results: Variance and sum entropy were the two most significant radiomic features that discriminated between pseudoprogression and true progression. P value, AUC, specificity and sensitivity were 0.03, 89.26%, 81.82%, and 100% respectively. Conclusions: Radiomic TA derived from perfusion images can be helpful in determining true versus pseudoprogression in GBM. Further, this study illustrates successful application of radiomic TA as an advanced processing step for different MRI perfusion maps (DCE, DSC).
Overall survival (OS) by line of therapy (LOT) in Medicare-enrolled glioblastoma multiforme (GBM) patients (pts).
Authors: Aly Abdalla , Singh Prianka , Korytowsky Beata , Dastani Homa , Ling Lisa , Botteman Marc , Norden Andrew David 
Published: September 2018

2039 Background: In clinical trials, the median OS of elderly GBM pts on standard treatment (tx) is ~9 months (mos) from diagnosis (dx), but has not been described in the real world (RW). This analysis describes RW OS for US Medicare GBM pts by LOT. Methods: GBM pts aged ≥66 years (y) were identified in SEER-Medicare (2007–2011). Pts were followed from dx to death, Medicare disenrollment or 12/31/2013. Systemic tx patterns were characterized as untreated (0L), ≥first line (1L+) and ≥second line (2L+). OS was estimated by the Kaplan-Meier method from dx for 0L, and from LOT start for 1L+ and 2L+. Results: Among 2533 eligible GBM pts (median age: 74 y; Charlson comorbidity index [CCI] ≥2: 13%), 49.9% received 1L+ and only 16.3% received 2L+. Median (1-year) OS for all pts was 5.3 mos (26%), range 1.6–10.7 mos (3–45%) depending on LOT, surgical resection (R) or Biopsy alone (B), tumor size, age, and CCI (Table). Conclusions: Receipt of tx has a significant impact on OS in Medicare GBM pts. This RW study shows that only 50% of pts receive tx, even though each LOT is associated with additional OS benefit. This suggests an unmet need for more efficacious therapies to allow additional treatment and improve outcomes. [Table: see text]
A novel MGMT methylation-based prognostic score in patients with glioblastoma.
Authors: Gerratana Lorenzo , Lombardi Giuseppe , De Carlo Elisa , Buoro Vanessa , De Maglio Giovanna , Marcato Raffaella , Isola Miriam , Cattaneo Monica , Bellu Luisa , Pelizzari Giacomo , Gurrieri Lorena , Follador Alessandro , Puglisi Fabio , Pizzolitto Stefano , Fasola Gianpiero , Zagonel Vittorina , Rizzato Simona 
Published: September 2018

2048 Background: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with improved outcome in glioblastoma (GBM) patients (pts). Pyrosequencing (PSQ) has been reported to be an accurate method for quantitative detection of CpG islands (CpGs) methylation, but the role of methylation heterogeneity among different CpGs sites is still unclear. Aim of this study was to evaluate on a large multicentric cohort a novel prognostic score based on the evaluation of the MGMT promoter methylation at 10 different CpGs sites. Methods: We retrospectively analyzed a series of 185 pts with GBM treated at the University Hospital of Udine and Istituto Oncologico Veneto in Padua between 2006 and 2015. The methylation level of 10 CpGs (74 – 83) was determined by PSQ. The cut-off point of 9% was used to define a CpG as methylated. One point was assigned to each methylated CpG, with a total score from 0 (all CpGs < 9%) to 10 (all CpGs ≥ 9%). A threshold capable to detect a favorable outcome (Overall Survival, OS > 24 months) has been identified through ROC analysis as 6 by a previous study conducted at our center. The prognostic impact was explored through Cox regression. Results: After a median follow-up of 59 months, the median OS and Progression Free Survival (PFS) in the whole population were 16.41 and 9.67 months, respectively. A score ≥ 6 identified pts with a considerably better median OS (24.85 vs 12.99 months, p < .0001) and PFS (11.44 vs 8.22 months, p < .0001). On multivariate analysis, it remained independently associated with a favorable prognosis (HR 0.38, 95% CI 0.27-0.55, p < 0.0001) after adjustment for IDH1 mutational status (HR 0.42, 95% CI 0.20-0.87, p = .02), age ( > 70 vs ≤ 70 years HR 2.20, 95% CI 1.48-3.28, p = .0001) and ECOG performance status (2-3 vs 0-1 HR 2.35, 95% CI 1.59-3.49, p < .0001). The score’s prognostic value was maintained in all the explored subgroups. Conclusions: Combining methylation data from multiple CpGs increases the prognostic value of the MGMT promoter methylation assessment. The study confirmed the independent prognostic value of a novel score system based on the evaluation of the MGMT promoter methylation at 10 different CpGi sites.
Number of tumor-infiltrating lymphocytes in breast cancer brain metastases compared to matched breast primaries.
Authors: Narloch Jessie , Luedke Catherine , Broadwater Gloria , Priedigkeit Nolan , Hall Allison , Hyslop Terry , Sammons Sarah LeNoir , Huggins-Puhalla Shannon Leigh , Leone Jose Pablo , Ramirez Juanita , Kirkpatrick John P , Ewend Matt G , Fecci Peter E , Brufsky Adam , Lee Adrian V. , Anders Carey K. , Blackwell Kimberly L. 
Published: September 2018

2049 Background: Breast cancer brain metastasis (BCBM) is frequent in advanced disease, has limited therapies, and is associated with poor prognosis. Increased stromal tumor infiltrating lymphocytes (sTILs) are prognostic in triple-negative breast cancer (TNBC) and predictive of therapeutic response in early breast cancer (BC). However, little is known about sTILs in the metastatic setting. We compared %sTILs between the largest known cohort of matched primary tumors and BCBM and correlated the results with clinical endpoints. Methods: We retrospectively investigated 37 matched primary tumors and BCBM tissue from three institutions. In addition, we identified 29 primary tumors from patients later diagnosed with BCBM. H&E-stained sections were manually measured for %sTILs using standard criteria. Wilcoxon signed rank tests assessed for changes in %sTILs between primary and metastatic lesions. A Cox proportional hazards model was used to determine if %sTILs in the breast tissue predicts time from primary tumor biopsy to diagnosis of brain metastasis (TTDBM) while adjusting for clinicopathologic features. Results: Average age at time of BCBM diagnosis was 53.6 (SD 12.3). 52% (34/66) of primary tumors were hormone receptor (HR) positive. Of 60 patients with known HER2 status, 28% (17) were HER2 positive and 40% (24) TNBC. Median %sTILS was significantly different between all primary tumors (15, IQR 5-20) and brain metastases (10, IQR 5-10), p = 0.001. The TNBC subtype (n = 11) showed the largest decrease in %sTILs between primary tumors (20, IQR 10-20) and brain metastases (5, IQR 5-10), p = 0.022. Comparing primary tumors and brain metastases, there was a 5% decrease in %sTILs in HR-/HER2+ (n = 5, p = 0.13) and HR+/HER2- (n = 7, p = 0.13), and a 5% increase in %sTILs in the HR+/Her2+ subtype (n = 9, p = 0.69). Percent sTILs in the primary tumors was not a significant predictor of TTDBM, when adjusting for race, age, HR status, and HER2 status, p = 0.87. Conclusions: BCBM have a significantly decreased %sTILs compared to their primary tumors, most prominent in TNBC. These results suggest altered tumor immunogenicity in the metastatic setting which has broad implications for the development of immunotherapy.