bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fosaprepitant use in children and adolescents at Memorial Sloan Kettering Cancer Center.
Authors: Liu Dazhi , Horiates Krisoula , Mathew Sherry , Pozotrigo Melissa , Thackray Jennifer , Kussin Michelle , Yan Shirley Qiong , Seyboth Brian M. , Modak Shakeel 
Published: September 2018

10575 Background: Recent NCCN guidelines recommend the addition of a neurokinin-1(NK1) receptor antagonist (e.g. fosaprepitant) to the serotonin 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist-corticosteroid combination for controlling both acute and delayed chemotherapy induced nausea and vomiting(CINV) associated with high emetogenic chemotherapy (HEC) in adults. Fosaprepitant is bioequivalent to aprepitant and could offer benefits to patients who are unable to tolerate oral antiemetics. However, little is known about the efficacy and safety of fosaprepitant in children. Methods: This retrospective chart review included all pediatric patients less than 18 years of age who received fosaprepitant at Memorial Sloan Kettering Cancer Center from July 2011 to November 2016. Results: Thirty-one patient charts representing a total of 105 doses of fosaprepitant were reviewed. Median age was 15 (range 2-17) years. Fifty-one doses (49%) were administered for primary prophylaxis for 11 patients; 40 doses (38%) for 12 patients who had a history of severe CINV and 14 doses (13%) as rescue for CINV in 10 patients after chemotherapy. Seventy-eight of the 101 chemotherapy cycles were highly emetogenic including 39 containing cisplatin. In the first two groups, patients did not have any episodes of vomiting in 97% and 88% of chemotherapy cycles respectively after fosaprepitant therapy. Seven of 12 patients receiving fosaprepitant for > 3 episodes of breakthrough vomiting within 24 hours had no vomiting episodes during the first 24 hours post fosaprepitant administration. No fosaprepitant-related side effects were reported. Conclusions: Fosaprepitant appears to be safe and tolerable in children with cancer in whom it may provide benefit as prophylaxis and treatment of CINV. However a phase III study is warranted to formally study its role in pediatrics.
Estimating the effects of patient-reported outcome (PRO) diarrhea and pain measures on PRO fatigue: Data analysis from a phase II study of abemaciclib monotherapy, a CDK4 and CDK6 inhibitor, in patients with HR+/HER2- breast cancer after chemotherapy for metastatic disease—MONARCH 1.
Authors: Boye Mark , Houghton Katherine , Stull Donald E , Ainsworth Claire , Price Gregory L 
Published: September 2018

1060 Background: Investigators reporting treatment-emergent adverse events (TEAEs) in the 3rdline or greater abemaciclib MONARCH1 Phase 2 study observed Grade 1-3 diarrhea, fatigue, and abdominal pain in 90, 65, and 39% of the patients (n = 132). Unknown is the extent that diarrhea and overall pain add to fatigue in this setting. Using patient-reported outcome (PRO) measures, we conducted cross-sectional and longitudinal multivariate analyses to estimate these effects. Methods: Data came from a single-arm, open-label study of previously-treated patients with mBC. Throughout the study, the Brief Pain Inventory and the EORTC QLQ-C30 v3 were co-administered. All constructs and items from these two questionnaires –except EORTC Items 25 and 28 (memory and financial difficulties) - were used to estimate the Structural Equation Model (SEM) and the direct and indirect effects of pain and diarrhea on fatigue. Extended pattern mixture modeling (ePMM) – a latent variable modeling method that allows the explicit analysis of missing data and identifies subgroups with differential changes over time – was used to explore these relationships from screening through cycle 8. Results: SEM results showed that at cycle 2 of treatment, pain was a significant predictor of fatigue (b = 0.68; P < 0.001; CI 0.48 – 0.90); diarrhea was not a significant predictor of fatigue (b = 0.06; P = 0.12; CI -0.04 – 0.17). ePMM results across eight 30-day cycles found three fatigue subgroups: no change, improvement, worsening then improvement. Belonging to a similar pain subgroup predicted belonging to the corresponding fatigue subgroup (ref class was no change; improving b = 5.03, P = 0.004; worsening b = 22.01, P < 0.001); the same was not true for diarrhea and fatigue (ref class was no change; improving b = 0.213, P = 0.75; worsening b = 0.04, P = 0.97). Conclusions: These results suggest that for patients undergoing 3rd line or greater mBC treatment, pain is a significant predictor of fatigue early and over the course of the trial. However, diarrhea is not a significant predictor of fatigue. Clinical trial information: NCT02102490.
Prognostic significance of tumor subtypes in women with breast cancer according to stage: A population-based study.
Authors: Leone Jose Pablo , Leone Julieta , Zwenger Ariel Osvaldo , Vallejo Carlos Teodoro , Leone Bernardo Amadeo 
Published: September 2018

1070 Background: Tumor subtypes (TS) are an important prognostic tool in breast cancer patients (pts). However, with contemporary therapies the prognosis of different subtypes is unclear. Recently, the AJCC proposed to incorporate TS among other variables in the 8th edition of the staging manual. The aim of this study was to analyze differences in overall survival (OS) by TS according to stage compared with other factors. Methods: We evaluated women with microscopically confirmed invasive breast cancer between 2010 and 2013 with known estrogen receptor (ER) and progesterone receptor (PR) (together hormone receptor [HR]) status and human epidermal growth factor receptor 2 (HER2) status reported to the SEER program. Pts with other primary either before or after breast cancer were excluded. Pt characteristics were compared between TS. Univariate and multivariate analyses were performed to determine the effect of each variable on OS. Results: We included 166,054 pts. Median age was 60 years (range 18-108). Median follow-up was 21 months (range 1-48). TS distribution was: 72.5% HR+/HER2-, 10.8% HR+/HER2+, 4.8% HR-/HER2+ and 12% triple negative (TN). Pts with HR+/HER2- tumors were older, had lower grade and presented with earlier stage (all p < 0.0001). OS at 3 years for each subtype according to stage is shown in the table (p for interaction < 0.0001). These differences in OS by TS continued to be significant for each stage in multivariate analysis adjusted for age, race, grade, histology and marital status. Conclusions: In this cohort, we observed significant differences in pt characteristics according to TS. Although HR+/HER2- tumors had better clinicopathologic features, the HR+/HER2+ group had the best OS in most stages. OS was significantly different by TS in each of the 4 stages and these results remained significant in the multivariate model. Pts with TN stage 1 tumors had similar OS as pts with HR+/HER2+ stage 2 tumors. Our results support the incorporation of TS as part of the staging variables in breast cancer. [Table: see text]
Retrospective-prospective blinded evaluation predicting efficacy of epirubicin by a multigene assay in advanced breast cancer within a Danish Breast Cancer Cooperative Group (DBCG) cohort.
Authors: Buhl Anna Sofie Kappel , Christensen Troels Dreier , Christensen Ib Jarle , Nelausen Knud Mejer , Balslev Eva , Knoop Ann S. , Brix Eva , Svensson Else , Glavicic Vesna , Luczak Adam , Langkjer Sven Tyge , Linnet Soeren , Jakobsen Erik , Bogovic Jurij , Ejlertsen Bent , Rasmussen Annie , Hansen Anker , Knudsen Steen , Nielsen Dorte , Jensen Peter Buhl 
Published: September 2018

1071 Background: Epirubicin remains a cornerstone in the treatment of primary and advanced breast cancer. This study evaluated the predictive effect of a multigene mRNA-based Drug Response Predictor (DRP) in the treatment of advanced breast cancer (ABC). We applied a mathematical method combining in vitro sensitivity with gene expression patterns in tumors. Previously the DRP has been broadly validated1, 2 including retrospective validation of epirubicin3. Methods: Among 838 consecutive patients from a DBCG cohort 137 patients were treated with epirubicin between May 1997 and November 2016 at one of the participating sites. Patients were examined every 9 to 12 weeks by CT scan and clinical evaluation. After patient informed consent, mRNA was isolated from formalin fixed paraffin embedded tumor tissue from diagnostic biopsies and analyzed using Affymetrix arrays. Blinded predictions of epirubicin efficacy were compared to clinical data collected retrospectively from patients’ medical records. Statistical analysis was done using Cox proportional hazards model adjusted for treatment line. Primary endpoint was progression free survival (PFS). Results: Median time to progression was 9.3 months (95% CI: 7.2-13.2). Of the 137 patients, four received epirubicin more than once. Scoring the DRP as a continuous covariate demonstrated that the DRP was significantly associated to PFS (p = 0.02). The estimated hazard ratio was 0.56 (90% CI: 0.35-0.89) comparing two patients with DRP score differing by 50 percentage points. The estimated median time to progression for a patient with a DRP value of 25% was 7 months versus 13 months for a patient with a DRP value of 75%. No interaction with previous adjuvant chemotherapy was observed (p = 0.98). Conclusions: The current study demonstrates a potential clinical value by being able to select patients that benefit from epirubicin against patients predicted not to benefit sparing the last patients unnecessary toxicity. Studies evaluating the predictor in an adjuvant setting will follow. 1 Knudsen et al PLoS ONE 9(2): e87415; 2 Buhl et al PLoS ONE 11(5): e0155123; 3 Wang et al JNCI 105(17): 1284-91
Characterization of bone only metastasis (BOM) patients (pts) with respect to tumor subtypes (TS).
Authors: Parkes Amanda Marie , Clifton Katherine , Al Awadhi Aydah , Oke Oluchi , Warneke Carla L. , Litton Jennifer Keating , Hortobagyi Gabriel N. 
Published: September 2018

1072 Background: Metastatic breast cancer (MBC) pts with BOM are a unique population with limited characterization. Our goal was to characterize the TS of BOM pts, evaluating differences in sites and types of bone metastases (BM), treatment, and survival. Methods: We identified pts followed at MD Anderson Cancer Center from 01/01/1997 to 12/31/2015 for at least 6 months with a BOM diagnosis as first site of metastasis (met). TS was assessed by initial biopsy immunohistochemistry (IHC) (Table 1) with hormone receptor (HR) + defined as ER or PR >10%. Results: We identified 1445 pts with BOM, 1049 with initial biopsy IHC available to group into TS (Table 1). Among BOM pts, the majority had multiple BM at diagnosis (1141/79%), most in both the axial (Ax) and appendicular (App) skeleton (53%). Of the 808 pts with BM categorized on imaging at diagnosis, the majority were lytic (389/48%), with 21% sclerotic, 18% mixed, and 12% blastic. Time from breast cancer diagnosis to first met differed significantly by TS, χ2(3) = 94.33, P< .0001, with median time to met longer for pts with blastic (3.08 years; 95% CI 2.03, 4.24) versus lytic lesions (1.75 years; 95% CI 1.27, 2.17). Conclusions: BOM patients are a unique MBC subpopulation, more commonly found in luminal TS patients. Our study demonstrates prognostic differences in BOM pts specific to TS and emphasizes the need for further study of BOM patients. [Table: see text]
Use of serial multi-template liquid biopsies in triple negative breast cancer monitoring.
Authors: Song Paul Y. , Simmons Jill , Dempsey Paul W. , Klem Erich , Carter Chris , Tahvilian Shahram , Scollick Brian , Strauss William 
Published: September 2018

1091 Background: Triple negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer in which up to 1/3 of all patients will relapse early and distantly. There remains no proven method to monitor and detect early recurrence. This study examines the utility of serial liquid biopsies using a multi-template approach (identification and analysis of cell-free DNA (cfDNA) and circulating tumor cells (CTCs)) as a solution. Methods: 210 patients (average 53 yrs.) with confirmed diagnosis of TNBC, within 3 years of completion of therapy (mean 25 mos.), and in full remission were enrolled. Liquid biopsies were performed quarterly to look for cancer specific genomic mutations not seen in germ line controls, but in cfDNA and CTCs using a custom 27-gene breast cancer panel. Prior validation of our gene panel demonstrated a false positive rate of 0.001-0.0007% in normal cfDNA and cell-based controls. Results: Each subject had on average 3.0 serial samples collected to date. 169 patients (80.4%) had evidence of mutations in at least one sample. Seventy-five percent of cfDNA and 36% of CTC samples examined have been found to bear mutations. The total number of samples with orthogonally (either between template or between draws) confirmed signal was 16.9%. Seven patients (3.3%) have developed documented evidence of recurrence, one in the axilla and the others with visceral/distant metastases. Of the patients that have recurred, all had a persistent mutation on consecutive blood draws or evidence of genomic mutations in both cfDNA and CTCs. Conclusions: The majority of TNBC patients in our study post-treatment were found to have genomic mutations on at least one liquid biopsy sample – either cfDNA or CTC. But, very few had a persistent presence of mutations in subsequent samples and 96.7% of our patients have remained NED. Unlike patients who remained NED, patients who recurred displayed persistent evidence of mutations on serial draws or in both cfDNA and CTC samples. To date our recurrence rate is lower than predicted. This study highlights the need for serial monitoring using a multi-template approach to better fully understand patient specific tumor biology and kinetics. The trial is ongoing. Clinical trial information: NCT02639832.
Immune gene signatures in triple-negative breast cancers characterized by varying levels of chromosomal instability.
Authors: Gyorffy Balazs , Bottai Giulia , Nagy Adam , Pusztai Lajos , Santarpia Libero 
Published: September 2018

1096 Background: Triple-negative breast cancer (TNBC) is generally characterized by high levels of chromosomal instability (CIN) and an intense immune infiltration. However, the link between these two hallmarks and its implications for clinical practice has not been fully elucidated. Methods: We generated eight immune metagenes representing various immune components: natural killer [NK], dendritic cells [DC], T-cells [TC], B-cells [BC], cytotoxic T-cells [CT], interferon [IFN], nuclear factor-κB [NF-kB], and macrophages [M]. Publicly available gene expression data from forty-two data sets, including 862 TNBC samples, were collected. TNBC tumors were clustered in three main subgroups (Basal-Like [BL1/2], Immunomodulatory [IM], and Mesenchymal/Mesenchymal Stem-Like [MS]) using transcriptomic profiling. The CIN70 signature was used to stratify TNBC patients according to the levels of CIN. Statistical analyses were performed using Mann–Whitney U test and Kaplan-Meier analyses. Results: The majority of TNBC samples showed a high level of CIN (83%), and several immune modules were differentially expressed between CIN-high and CIN-low tumors. Specifically, CT, NK, DC, M, and NF-kB signatures were overexpressed in CIN-low TNBC ( p < 1.0E-04). We then evaluated the distribution of genomic instability among TNBC molecular subgroups. Noteworthy, the CIN-high group was composed by a comparable proportion of BL1/2 (39%) and MS (35%) tumors, while CIN-low TNBCs were consistently enriched for MS cancers (61%). Higher expression of the NK, M, and IFN metagenes lead to better survival in CIN-high tumors ( p = 1.9E-02, p = 2.1E-04, and p = 1.1E-03, respectively). Only IFN had the same correlation to survival in CIN-low ( p = 1.4E-02). Conclusions: TNBCs with low levels of CIN may principally enclose M/MSL tumors, which are characterized by an intense immune infiltration and overall good prognosis. Conversely, the TNBC CIN-high group is more heterogeneous in terms of both biological features and levels of immune infiltrates. Therapeutic strategies to promote and boost immune response in the genomically unstable TNBC subgroup warrant further investigation.
Influence of marital status on risk of mortality for 23,493 cases of triple negative breast cancer for four mutually exclusive race/ethnicities.
Authors: Parise Carol , Caggiano Vincent 
Published: September 2018

1098 Background: Marital status has been associated with better breast cancer survival. However, breast cancer is a heterogeneous disease and it has not been determined whether marital status is a survival advantage for women with triple negative breast cancer (TNBC) and if this advantage holds for all race/ethnicities. The purpose of this study was to determine if being unmarried resulted in an increased risk of mortality for TNBC for four mutually exclusive race/ethnicities. Methods: We identified 23,493 cases of TNBC from the California Cancer Registry 2000-2014. Marital status at time of diagnosis was defined as: 1) married, 2) single, never married; 3) separated; 4) divorced; 5) widowed. Race/ethnicity was defined as white (n = 13,241), black (n = 2,775), Hispanic (n = 5,059), and Asian/Pacific Islander (API) (n = 2,418). Kaplan-Meier Survival Analysis and Cox Regression were used to assess the risk of mortality associated with marital status using married as the reference category. Marital status was considered a risk for mortality and hazard ratios (HR) and 95% confidence intervals reported if the Wald χ2 was statistically significant (p < 0.05). Models were adjusted for AJCC stage, age, grade, socioeconomic status, and treatment. Separate analyses were conducted for each race/ethnicity. Results: For allraces, single women had statistically significantly worse unadjusted survival (p < 0.05) than married women. However adjusted analyses showed that single (HR = 1.13; 1.01-1.27) and widowed (HR = 1.43; 1.27-1.61) white women had increased mortality when compared with married women. Single (HR = 1.50; 1.14-1.96) and divorced (HR = 1.75; 1.23-2.48) API women had an increased risk of mortality compared with married women. For black and Hispanic women, marital status was not associated with risk of mortality. Conclusions: Being married at the time of diagnosis of TNBC is a survival advantage only for white and API women but not for black and Hispanic women.
Beyond triple-negative breast cancer and African ancestry: Tumor phenotypes among internationally diverse patient populations.
Authors: Jiagge Evelyn Mawunyo , Jibril Aisha , Divine George , Gyan Kofi K. , Bensenhaver Jessica Miley , Oppong Joseph Kwaku , Awuah Baffour , Adjei Ernest , Merajver Sofia , Wicha Max , Newman Lisa A. ,   Henry Ford Health System International Center for the Study of Breast Cancer Subtypes
Published: September 2018

1101 Background: Population-based incidence rates of breast cancers that are negative for estrogen receptor (ER), progesterone receptor (PR), and HER2/ neu(triple negative breast cancer {TNBC}) are higher among African American (AA) compared to White American (WA) women. Several studies show higher TNBC frequency among selected populations of African patients. The colonial-era trans-Atlantic slave trade resulted in shared West African ancestry between contemporary AA and Ghanaian (Gh) populations. The extent to which TNBC susceptibility is related to East African versus West African ancestry, and whether these associations extend to expression of other biomarkers such as Androgen Receptor (AR) and mammary stem cell marker ALDH1 is unknown. Methods: We used immunohistochemistry to assess ER, PR, HER2/ neu, AR and ALDH1 among WA (n = 153); AA (n = 76); Ethiopian (Eth)/East African (n = 90) and (Gh)/West African (n = 286) breast cancers through an IRB-approved international research program. Results: Mean age at breast cancer diagnosis was 43; 49; 60; and 57 years for the Eth; Gh; AA; and WA patients, respectively. Frequency of TNBC was significantly higher for AA and Gh patients (54% and 41%, respectively) compared to WA and Eth patients (23% and 15%, respectively); p < 0.001. These associations were unchanged when limited to patients age 50 and younger (47% and 49% for AA and Gh, respectively; versus 18% and 16% for WA and Eth, respectively); p < 0.001. Frequency of ALDH1 positivity was also higher for tumors from AA and Gh patients (32% and 36%, respectively) compared to those from WA and Eth patients (23% and 17%, respectively); p = 0.007. Significant differences were observed for distribution of AR positivity, which was 71%; 55%; 42% and 50% for the WA; AA; Gh; and Eth cases, respectively (p = 0.008). Conclusions: We found a correlation between extent of African ancestry and risk of particular BC phenotypes. West African ancestry was associated with increased risk of TNBC and breast cancers that are positive for ALDH1. Future studies of hereditary TNBC susceptibility among women with African ancestry are warranted.
Clinical, radiological and genetic features, associated with the histopathologic response to neoadjuvant chemotherapy (NAC) and outcomes in locally advanced soft tissue sarcoma (STS) patients (pts).
Authors: Cousin Sophie , Crombe Amandine , Stoeckle Eberhard , Brouste Véronique , Le Loarer Francois , Lucchesi Carlo , Kind Michèle , Toulmonde Maud , Sargos Paul , Michot Audrey , Kantor Guy , Soubeyran Isabelle , Coindre Jean Michel , Italiano Antoine 
Published: September 2018

11014 Background: Two large phase III studies have shown an improved overall survival in soft-tissue sarcoma (STS) pts treated with neoadjuvant chemotherapy. The prognostic impact of pathologic response is not known neither the clinical, radiological and genetic features associated with response. Methods: Data from pts with localized STS of the extremities or trunk wall and treated with anthracyline-based NAC at Institut Bergonie (Bordeaux, France) were reviewed. Central pathology (diagnosis, histological response) and radiology (MRI, DCE-MRI) reviews were performed for all the cases. A good histological response (GR) was defined as <10% residual viable tumor. Exome and RNA sequencing of pre-treatment tumor samples was performed in order to identify genetic aberrations predictive of response. Results: 150 patients (88 male) were included in the study. Median age was 60 years (17-84). 40 pts (26.7%) were good responders. GR was associated with undifferentiated pleomorphic sarcomas and very large tumors (> 20 cm). Median OSwas 10.3 year [IC95 : 5.8 ; 14.9]. On multivariate analysis, only GR (HR= 0.36, 95%CI 0.184-0.703, p=0.0028) and performance status (PS) (HR= 3.799, 95%CI 1.72-8.387, p=0.001 for PS=2-3) were prognostic factors for OS. Early DCE- MRI parameters (after 2 cycles of treatment) such as, area under the contrast concentration vs. time curve for 90 seconds after contrast injection ( IAUC90) were strongly associated with histological response (p=0.027) whereas RECIST 1.1 was not. Conclusions: As for bone sarcomas, histological response to NAC is a crucial prognostic factor in STS. Multiparametric MRI parameters obtained post-2nd cycle of NAC are predictive of histological response and should be considered to adjust the therapeutic strategy. Genetic features (including the CINSARC signature) associated with response to NAC will be presented at the meeting.