bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utility of 2D-speckle tracking echocardiography in early identification of left ventricular dysfunction in antineoplastic therapy-induced cardiotoxicity.
Authors: Coppola Carmela , Tocchetti Carlo G. , Piscopo Giovanna , Cipresso Clemente , Maurea Carlo , Lombari Maria Cristina , Rea Domenica , Maiolino Piera , Monti Maria Gaia , Tarantini Luigi , Russo Giulia , Cioffi Giovanni , Giotta Francesco , Oliva Stefano , Capasso Immacolata , Iaffaioli Rosario Vincenz , Arra Claudio , Maurea Nicola 
Published: March 2020

631 Background: ErbB2 is overexpressed in about 25% of breast cancers; in the heart, it modulates myocardial development and function. Trastuzumab (T), an anti-ErbB2 inhibitor, has improved the prognosis of patients with breast cancer, but is related to an increased risk of asymptomatic left ventricular (LV) dysfunction (3-34%) and heart failure (2-4%). Conventional measures of ventricular function, such as fractional shortening (FS) and ejection fraction (FE) are insensitive in detecting early cardiomyopathy induced by antineoplastic therapy. Aim of this study is to evaluate whether myocardial strain by 2D-speckle tracking (ST) is able to identify early LV dysfunction in mice treated with doxorubicin (D) and T, alone or in combination (D+T) and to relate data of cardiac function with tissue alterations. Methods: Cardiac function was measured with FS, by M-mode echocardiography, and with radial myocardial strain with ST in sedated C57BL/6 mice (8-10 wk old) at time 0, 2 and 6 days of daily administration of D, T, D+T and in a control group. In excised hearts, we evaluated TNFα and CD68 by immunohistochemistry; interstizial fibrosis was analyzed with picrosirius red staining. Results: FS was reduced in group D and D+T at 2 days (52+0.2% and 49+2% respectively), both p<0.001 vs 60+0.4% (sham), while in group T it decreased only at 6 days (49+1.5% vs 60+0.5%, p=.002). In contrast, after 2 days, myocardial strain was already reduced not only in D and D+T, but also in T alone: 43+3%, 49+1%, and 44+7%, respectively, all p<0.05 vs sham (66+0.6%). Cardiotoxicity was associated with significant alterations in extracellular matrix remodeling as confirmed by an increase of interstizial collagen with D (4.56%), T (2.17%) and D+T (3.77%)at 6 days p<0.05 vs sham (1.17%) and by increased cardiac inflammation in fact the myocytes were positive for TNFα and CD68 cells/mm2at 6 days in group D (16.46% and 155 respectively), in group T+D (12.35% and 74.16) and in group T (5.65% and 72.32) p<0.01 vs sham (0.56% and 2.3). Conclusions: Myocardial strain identifies LV systolic dysfunction earlier than conventional echocardiography and can be a useful tool to predict cardiotoxicity in this setting.
Identification of patients at high risk of recurrent disease development by detection of HER2-positive disseminated tumor cells in bone marrow of patients with HER2-negative tumors.
Authors: Aft Rebecca , Mudalagiriyappa Chidananda , Pillai Sreeraj , Trinkaus Kathryn , Fleming Timothy , Watson Mark 
Published: March 2020

633 Background: A subpopulation of patients with HER2-negative tumors benefit from HER2 therapy. HER2 expression can be discordant between primary tumors and metastases. We have examined the bone marrow (BM) of early stage breast cancer patients for HER2-expression by disseminated tumor cells (DTCs) and the association with disease recurrence. Methods: BM was collected from clinical stage II-III breast cancer prior to treatment between 2007-2011. Gene expression of ERBB2 was determined by multiplex PCR (Fluidigm Biomark [FB]). Positive expression was defined as at least 1.4 fold above a pool of normal BM. Expression was confirmed by single gene PCR and Nanostring nCounter (NC) assays. Cox proportional model was used to estimate hazard ratios (HR). Results: BM from 74 patients was analyzed. Median follow-up was 3.4 years (range 8 months-84 months). 24% of the patients developed metastatic disease. For ERBB2 detection, there was excellent correlation between NC and the FB assays (kappa=0.87, 95% CI [0.62, 1.00]). Nine patients expressed ERBB2 in their BM. Five of the 9 patients had Her2-positive tumors and were treated with trastuzumab. One of 5 (20%) of these patients relapsed whereas 75% (3 of 4) of the patients with HER2-negative tumors but ERBB2-positive DTCs relapsed. Patients with HER2-negative tumors/ERBB2-positive BM were found to have a greater hazard of recurrence than patients with HER2-negative tumors/ERBB2-negative BM or ERBB2-positive DTCs treated with trastuzumab (p=.0069; Table). Those patients with ERBB2-positive BM who did not receive trastuzumab had a decreased disease free survival (p=.016). Conclusions: We have found discordant expression of HER2/ERBB2 in tumors and BM of stage II-III breast cancer patients. The presence of ERBB2 expressing DTCs in patients with HER2-negative tumors identifies a subset of patients at increased risk of recurrence who may benefit from targeted HER2-therapy. [Table: see text] .
A Bayesian meta-analysis of the prognostic value of circulating HER2/neu levels in breast cancer (BC) patients.
Authors: Carney Walter P. , Thiel Robert , Bernhardt Dirk , Ali Suhail M. , Leitzel Kim , Lipton Allan 
Published: March 2020

643 Background: Many reports have shown the prognostic value of HER-2 measured in tumor tissue or in blood. In 2009, Finn et.al. showed that in a study of 579 MBC patients whose serum HER-2 levels (sHER-2) were constantly below normal had a longer PFS than patients with a sHER-2 level constantly above normal. Patients who converted from above normal to less than normal during therapy had a longer PFS than the opposite change. Methods: We performed a Bayesian meta-analysis of 12 studies where all sHER-2 levels were measured using an FDA cleared sHER-2 test with a standard cutoff of 15ng/ml. We chose a Bayesian approach because a “meta-analysis” is a natural extension of the Bayesian view that current knowledge is the result of prior knowledge modified by the data. After an in depth literature search, we selected 12 publications based on the following criteria. Baseline levels were available from either early stage or late stage patients who had at least a 2 year disease free or progression free survival as indicated by a Kaplan-Meier (K-M) curve. Results: The analysis included 4030 BC patients of which 1106 patients had baseline levels < 15ng/ml and 2924 patients had baseline values >15ng/ml. From the K-M curves, we estimated the number of recurrences up to 24 months in each group and prepared a 2x2 table for each study. We determined the odds ratio (OR) for the 12 studies which ranged from 0.57 to 74. A posterior distribution for the aggregated 12 studies can be represented by a Dirichlet distribution. 10,000 estimates of the aggregated OR indicated that there is a 95% credibility that the odds of a woman with baseline sHER-2 >15ng/ml recurring at or before two years is between 3.39 and 4.57 times higher than the odds of a woman whose baseline sHER-2 was < 15ng/ml recurring at or before two years. Conclusions: This meta-analysis agrees with previous studies that serum HER-2 levels > 15ng/ml can be a strong prognostic indicator for women with Breast Cancer and that managing therapy regimens to maximize the decrease in serum HER-2 levels could be important target in treating patients.
Exposure–efficacy relationship of trastuzumab emtansine (T-DM1) in EMILIA, a phase III study of T-DM1 versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC).
Authors: Wang Bei , Jin Jin , Wada Russell , Fang Liang , Lu Dan , Guardino Ellie , Swain Sandra M. , Untch Michael , Girish Sandhya 
Published: March 2020

644 Background: T-DM1 is an antibody–drug conjugate composed of trastuzumab (T), a stable thioether linker, and the potent cytotoxic agent DM1. In the phase III study EMILIA, median PFS and OS were significantly prolonged with T-DM1 vs XL in patients (pts) with HER2-positive locally advanced or MBC previously treated with T and a taxane; (PFS hazard ratio [HR]=0.65, p<0.001; OS HR=0.68, p<0.001). We report the effects of T-DM1 exposure on efficacy outcomes in EMILIA. Methods: In EMILIA, pts were randomized 1:1 to receive T-DM1 3.6 mg/kg q3w (n=495) or XL (n=496) in 21-day cycles. Pharmacokinetic (PK) samples were from cycle 1 (n=350, T-DM1 arm only). Exposure variables were T-DM1 AUC, T-DM1 Cmin, total T AUC, and DM1 Cmaxcalculated by noncompartmental analysis. A logistic regression model was used to evaluate the relationship between T-DM1 exposure and objective response rates (ORR) in the T-DM1 arm. Multivariate Cox proportional hazards models were used to calculate HRs of OS and PFS for each T-DM1 exposure quartile vs all randomized pts in the XL arm, adjusting for baseline covariates. Results: For ORR, mean T-DM1 AUC was 536 day*ug/mL for responders and 502 day*ug/mL for non-responders (P=0.09); mean DM1 Cmax was 4.55 ng/mL and 4.64 ng/mL, respectively (P=0.64). OS and PFS HRs (and 95% CIs) of T-DM1 vs XL stratified by T-DM1 exposure quartiles are shown (Table). Conclusions: In EMILIA, no clear trends were observed between T-DM1 exposure and PFS, OS, or ORR, following administration of T-DM1 3.6 mg/kg q3w. However, there was a suggestion of improved OS HR by stratified T-DM1 Cmin quartiles, albeit with mostly overlapping 95% CIs. Ongoing T-DM1 clinical trials will further evaluate this potential relationship. [Table: see text]
Impact of copayment elimination on annual and biennial screening mammography utilization among rural U.S. women.
Authors: Peppercorn Jeffrey M. , Wheeler Stephanie B. , Houck Kevin , Peterson Bercedis , Villagra Victor , Antetomaso James , Wogu Adane Fekadu , Lyman Gary H. 
Published: March 2020

6503 Background: Early detection of breast cancer through mammography screening leads to earlier stage at diagnosis and improved survival. Previous research has shown that rural American women are less likely to receive screening mammography compared to their urban counterparts. Copayments for mammography are a potential barrier to screening, and elimination of copayments may improve screening rates. We examined annual (aSMU) and biennial (bSMU) screening mammography utilization and the impact of copayment elimination among rural U.S. women. Methods: Using the insurance claims database of the National Rural Electric Cooperative Association (NRECA), which insures over 100,000 electrical workers and their families nationally, we identified all women ages 40 to 64 with no prior history of invasive breast cancer or DCIS (based on ICD-9 codes) and captured claims for aSMU and bSMU between 1999 and 2009. Changes in screening over time were assessed for the periods before and after NRECA elimination of copayments for screening mammography in January, 2006. Chi-squared tests were used to compare aSMU and bSMU rates by age group. All p-values are two-sided. Results: During this time period, over 20,000 women ages 40 to 64 received health insurance through NRECA each year. From 1999 to 2009, aSMU increased from 38.1% to 49.5%, while bSMU increased from 57.2% to 68.1%. Screening increased significantly following elimination of copayments in 2006 (p = 0.0004). Specifically, for the period 2006-2007 compared to 2004-2005, the percentage of women undergoing at least biennial screening increased from 60.9 to 68.8% (p < 0.0001), with absolute differences in screening by age ranging from an increase of 5.3% among women 40-45, to 10% among women 60 – 64. Conclusions: Evaluation of insurance claims data from rural US populations reveals that a large percentage of rural women ages 40 to 64 do not undergo even biennial breast cancer screening. Elimination of copayments improves both annual and biennial screening rates in all age groups, but does not eliminate all barriers. Further investigation is ongoing to understand financial and non-financial barriers to screening and attitudes towards current screening recommendations.
Accuracy and completeness of diagnosis codes for cancer metastasis on Medicare claims.
Authors: Chawla Neetu , Yabroff K. Robin , Mariotto Angela , McNeel Timothy S. , Schrag Deborah , Warren Joan L 
Published: March 2020

6521 Background: Researchers are increasingly using diagnosis codes from administrative claims for cancer patients to identify metastatic disease at initial diagnosis or recurrence. However, the validity of metastasis codes on claims has not been established. We used the linked SEER -Medicare data to assess the completeness and validity of metastasis codes from Medicare claims for three common U.S. cancers. Methods: The study included 80,052 breast, lung, and colorectal cancer patients diagnosed with localized, regional, or distant disease in the SEER data between January 1, 2005 and December 31, 2007. From Medicare claims, patients were classified as having regional or distant disease at diagnosis if they had one hospital claim or two physician claims with metastasis codes within 3 months of diagnosis. Patients without claims with metastases codes were classified as having local disease. Using SEER data as the gold standard, we calculated sensitivity, specificity, positive and negative predictive values of metastasis codes on Medicare claims. We conducted multivariate logistic regression analysis to evaluate patient factors associated with stage misclassification for each cancer site. Results: For patients with distant disease per SEER data, the sensitivity and PPV of the claims to identify distant disease was: breast (50.6%, 67.3%), colorectal (72.2%, 68.8%) and lung cancer (42.1%, 88.6%). None of the measures for stage simultaneously exceeded 80% for sensitivity, specificity, and PPV for any of the cancer sites. In adjusted analysis, older, lower-income, and African American patients were more likely to have stage at diagnosis misclassified from Medicare claims. Conclusions: Use of diagnosis codes alone in Medicare claims will misclassify stage at diagnosis for cancer patients, particularly for patients with metastatic disease. Our findings also suggest that using diagnosis codes for metastasis to define recurrence in Medicare claims will be limited.
Black-white disparity in physical performance among older women with breast cancer: The role of physical activity and inflammation.
Authors: Owusu Cynthia , Schluchter Mark D. , Koroukian Siran M. , Schmitz Kathryn , Berger Nathan A. 
Published: March 2020

6525 Background: Compared with non-Hispanic Whites (NHW), African-Americans (AA) experience poorer physical function. However, little is known about the existence of racial disparity in physical performance among older adults with cancer, and clinical factors that might explain such differences. Methods: This is a cross-sectional study of women ≥ 65 years (n=108), with stage I-III breast cancer. Before adjuvant treatment, participants completed the Short Physical Performance Battery (SPPB), an objective measure of lower extremity function on a scale of 0-12, with higher scores denoting higher physical performance. Self-reported physical activity was ascertained with the Minnesota Leisure Time Activity Questionnaire. Serum level of C-reactive protein (CRP) was determined and log transformed for analyses. Results: The median age was 74.0 years (range 65-93 years) and 32% were AA. The mean SPPB score was 8.5 (SD 3.5). Compared to NHW, AA had lower mean SPPB scores (7.0 vs. 9.2, p=0.002), were less physically active (8.2 vs. 19.4 MET-hours/week, p=0.005), and had higher mean serum CRP(log) (-0.43 vs. -0.86, p=0.002). In multivariate linear regression analysis that accounted for age, educational status, comorbidities and geriatric syndromes, AA race relative to NHW was independently associated with decreasing SPPB scores, [beta coefficient = -1.67, SE: 0.57, p=0.004]. When differences in serum CRP and physical activity were accounted for in the model, increasing CRP and decreasing physical activity were independently associated with decreasing SPPB scores, and eliminated the racial difference in physical performance by 23% and 40%, respectively. This suggests sub-clinical inflammation and physical activity mediate the relationship between race and physical performance. Conclusions: Among older women with breast cancer, racial disparity in physical performance may be reduced through increased physical activity and therapeutic strategies that moderate sub-clinical inflammation. Given the clinical importance of functional status in cancer treatment decision-making, interventions directed at attenuating racial disparity in physical performance are warranted.
The role of families in decisions about cancer treatments.
Authors: Soriano Gabriela , Landrum Mary Beth , Weeks Jane C. , Arora Neeraj K , Malin Jennifer , Ganz Patricia A. , van Ryn Michelle , Keating Nancy Lynn 
Published: March 2020

6528 Background: Shared decision-making is an important component of patient-centered care and is associated with improved health outcomes. Little is known about patients’ involvement of family members in decisions about cancer treatments or whether family involvement varies by patient demographic or clinical characteristics. Methods: Data for this study were collected as part of the Cancer Care Outcomes Research and Surveillance (CanCORS) study, a large multi-regional prospective cohort study of cancer care and outcomes of lung and colorectal cancer patients. Patients were surveyed about the roles of their families in decisions about surgery, radiation, and/or chemotherapy. We used multinomial logistic regression to identify patient factors independently associated with family roles in decisions. Results: Among 5284 patients, 28.5% reported little or no family input in decisions, 22.1% reported making decisions after considering the family’s opinion, 47.9% reported the patient and family made decisions together, and 1.5% reported the family made decisions. In adjusted analyses, married, female, older, and insured patients were more likely to report making decisions with their family (all P<.001). Family involvement varied substantially by race/ethnicity and language, with Chinese-speaking Asian (63.5%) and Spanish-speaking Hispanic (56.8%) patients reporting making decisions with their family more often than English-speaking Hispanic patients (48.5%) and whites (48.3%). Patients from Veterans Affairs hospitals were least likely to report making decisions together with family (P<.001). Family involvement varied statistically by cancer type, stage, comorbidity, health status, and depression, but differences were minimal. Conclusions: Most patients with a new diagnosis of lung or colorectal cancer involve family members in treatment decisions. Certain groups, such as non-English speaking Hispanics and Asians rely significantly on family; for these groups, it is important that physicians inquire about patients’ preferences for family involvement and work to integrate family members in decisions accordingly. Further studies are needed to determine the impact of family involvement in treatment decisions on oncology outcomes.
Geographic variation in the adjuvant treatment of NSCLC over time.
Authors: Schroeder Mary C. , Tien Yu-Yu , Halfdanarson Thorvardur Ragnar , Abu Hejleh Taher , Nattinger Matthew , Brooks John 
Published: March 2020

6542 Background: Adjuvant chemotherapy (ACT) and postoperative radiotherapy (PORT) are used in the treatment of resected NSCLC to reduce risk of relapse, but guideline-based recommendations for these treatment modalities have varied over time. ACT is now recommended for stage II-IIIA NSCLC following resection based on phase III trial results which, starting in 2003, showed improved survival. Conversely PORT recommendations have been rescinded due largely to a 1998 Lancet meta-analysis. In this study we explore the rates of these two adjuvant treatment modalities across areas over time. Methods: Using SEER-Medicare data we identified 18,410 patients diagnosed 1992-2007 with resected NSCLC. Adjuvant treatment was defined as the first treatment received within 4 months of surgery. The study period was divided into 3 eras: 1992-1998, 1999-2003, and 2004-2007. Area treatment rates were calculated using the 50 patients closest to each zip code, adjusting for patient and area characteristics. Areas were then ranked and divided into quintiles. Percent differences were calculated to measure the variation between the highest and lowest quintiles. Results: Between 1992-1998 when the results of the phase III ACT trials were still unknown and utilization of ACT was low, areas with the highest treatment rates were 35 times more likely than areas with the lowest rates to administer ACT. After 2003 ACT use increased swiftly and geographic variation fell. In contrast, PORT utilization rates have declined and become more geographically dispersed since 1998. Receiving no adjuvant treatment was highest between 1999-2003, after the Lancet PORT meta-analysis and before the major ACT trials. Conclusions: NSCLC adjuvant treatment has been shifting from PORT to ACT. The positive results of the ACT trials and publication of treatment guidelines have increased usage and reduced geographic variation in ACT use. Geographic variation in PORT use however has increased over time, although overall usage has decreased. [Table: see text]
Cost-effective analysis of the use of EGFR inhibitors (E) for wild-type (WT) KRAS unresectable metastatic colorectal cancer (mCRC).
Authors: Riesco Martinez Maria C. , Berry Scott R. , Ko Yoo-Joung , Mittmann Nicole , Lien Kelly , Hassan Shazia , Giotis Angie , Chan Kelvin K. 
Published: March 2020

6552 Background: Patients (pts) with unresectable WT KRAS mCRC benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev) and E. The most cost-effective strategy to combine them remains unclear. Methods: A Markov model was constructed for a hypothetical cohort of pts with mCRC to examine the costs and outcomes of 3 treatment strategies: (A): 1st line (1L) Bev+FP+O/I, 2nd line (2L) FP+I/O, 3rd line (3L) E, (B): 1L Bev+FP+O/I, 2L FP+I/O, 3L E+I, and (C): 1L E+FP+O/I, 2L Bev+FP+I/O, 3L best supportive care (BSC). Efficacy and probability data of the treatments were obtained from clinical trials identified through a systematic review of the literature. Resource utilization data were derived from a chart review of 65 consecutive pts treated at Odette Cancer Centre (OCC) since 2009 and from the literature. Utilities were obtained by surveying oncologists (n= 24) across Canada using EQ-5D. Costs were obtained from the Ontario Ministry of Health and Long/Term Care, Ontario Case Costing Initiative, OCC and the literature. The analysis was conducted from the Canadian public healthcare system perspective over a 5 year time horizon with a 5% discount in 2012 Canadian dollars (CAD$) for cost and outcome. Incremental cost-effectiveness analyses were conducted comparing costs and outcomes of the 3 strategies. One way and probabilistic sensitivity analyses (SA) were conducted (n=10,000). Results: All 3 strategies appeared to be of relatively similar efficacy clinically, but C is more expensive than A or B by >45% (see Table). The model is primarily driven by the acquisition cost of drugs. B is most cost-effective when the willingness-to-pay (WTP) threshold >$120,000/QALY. SA showed that C would be cost-effective only when the progression-free survival of E is better than Bev in 1L with hazard ratio <0.24 at WTP of $150,000/QALY. Conclusions: 1L use of E followed by 2L Bev in mCRC is not cost-effective at the current pricing of E relative to Bev. [Table: see text]