bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal modeling with SimBioSys TumorScope to predict chemotherapeutic response in breast tumor microenvironments.
Authors: Mamillapalli Chaitanya K , Markwell Timothy K , Ellis Jason K , Pfiefer John , Pandey Tushar , Cole John A , Peterson Joseph R , Fox Daniel J 
Published: May 2020

e12656 Background: Predictive models of the efficacy of different tumor therapies will provide significant enhancements to current standard of care practices. Predicting a given tumor’s growth and treatment response, however, is an intricate process that requires not only an understanding of the tumor's intrinsic characteristics, but also spatial- and temporal-resolved tumor shape descriptions, surrounding tissue dynamics, and a complete account for the milieu of diffusible molecules that drive tumor behaviors and interactions. Here we report an ongoing retrospective study designed to validate SimBioSys TumorScope as a computational tumor therapy prediction model in a real-world clinical setting. Methods: Fully-deidentified and HIPAA-compliant data were assessed from real-world clinical records and cases. Subjects comprised early stage breast cancer patients who were treated with neoadjuvant chemotherapy (NACT) and subsequent surgical resection. Data fields included imaging data, biomarker status, tumor sizing, demographic data, digital pathology, and genetic lab test data. Half of the data, including all data fields, were used as a training dataset for TumorScope. The second half of the data, with blinded diagnoses and results, will be used to test TumorScope’s prediction accuracy. Simulations will be initialized with pre-treatment MRI data and processed through the entirety of each patient's specified treatment regimen. Predicted tumor volume and longest dimension will be compared against measured values at several time-points after therapy initiation. Overall accuracy will be statistically assessed by the Pearson correlation coefficient between predicted and measured tumor volume and longest dimension at each time-point, as well as their root-mean-squared-errors. Results: Final statistical analysis is currently underway. Thus far, SimBioSys TumorScope has trended high accuracy levels with the non-blinded “training” cohort just as it has in previous database studies, with a Pearson correlation coefficient greater than 0.94. Conclusions: SimBioSys TumorScope for Breast Cancer accurately predicts patient NACT responses via spatio-temporal modeling of drug and nutrient perfusion, metabolic behavior, and the physio-chemical interactions between surrounding tissues. Future prospective studies may assess TumorScope’s capacity to support efficient patient treatments and enhance overall standard of care.
Targeted therapies: How can CT imaging improve evaluations and help understand mechanism of drug action?
Authors: Beaumont Hubert , Iannessi Antoine , Chamorey Emmanuel , Faye Nathalie , Klifa Catherine , Hsieh Chih-Yi 
Published: May 2020

e13012 Background: We compared the therapeutic response between Varlitinib plus Capecitabine (VC) and Lapatinib plus Capecitabine (LC) by stratifying changes in tumor’s longest diameter (LD) and volume (VOL) per tumor location in patients with HER2+ metastatic breast cancer after trastuzumab therapy. Methods: We retrospectively analyzed the ASLAN001-003 double-arm trial (NCT02338245). We first tested the intra and inter-arm equivalence in number and size of tumors at each location of the disease.Second, we compared the inter-arm average changes in 1) tumor burden according to RECIST; 2) stratified tumor burden in summing, for each patient, the target lesions from the same organ locations; 3) tumors considered independent but grouped per organ location of the disease.Third, we tested the intra-arm differential responses of pairwise groups of tumor locations: breast-lung, breast-liver, breast-lymph nodes, lung-liver, lung-lymph nodes and liver-lymph nodes. A sensitivity analysis tested the robustness of our results. Results: We followed 74 tumors in 35 patients (14 VC; 21 LC) after 12 weeks of treatment. Primary breast tumors had a larger size than metastasis (p < 0.002). Tumor proportions at each organ location of the disease were not significantly different. The inter-arm difference in changes of tumor burden yielded: p = 0.086 (LD) and p = 0.13 (VOL); in stratifying patients per breast tumors: p = 0.002 (LD) and p < 0.001 (VOL); and for independent breast tumors: p = 0.001 (LD) and p < 0.001 (VOL). We found differential responses in the LC arm for breast-liver (p = 0.007 (VOL)) and Liver-Lymph node (p = 0.06 (VOL)). After outlier’s removal, the inter-arm difference was confirmed for breast tumors (p = 0.004 (LD); p < 0.001 (VOL)) and when considering all tumors as independent (p < 0.01(LD); p = 0.04 (VOL)). The differential Breast-Liver response in the VC arm was confirmed p < 0.05 (LD or VOL). Conclusions: Differential imaging responses were found across treatment arms and tumor locations. The stratification of changes provides new insights into responses of targeted therapies and more accurate drug comparisons. The stratification is a promising approach to better understand therapy mechanisms of action behind tumor heterogeneity.
Pyrotinib combined with capecitabine as first-line therapy for HER2-positive metastatic breast cancer: A pooled analysis of three randomized controlled trials.
Authors: Jiang Zefei , Xu Binghe , Yan Min , Ouyang Quchang , Hu Xi-Chun , Li Wei , Feng Ji Feng , Zhang Qingyuan , Tong Zhongsheng , Yan Ping , Zhu Xiaoyu , Rong Shangyi , Zou Jianjun 
Published: May 2020

e13022 Background: Anti-HER2 agents combined with chemotherapy is the treatment strategy for treatment-naive HER2-positive relapsed or metastatic breast cancer. This pooled study was conducted to investigate the efficacy of pyrotinib plus capecitabine as first-line treatment in patients with HER2-positive relapsed or metastatic breast cancer. Methods: Data were derived from three randomized controlled trials. In the phase 2 (NCT02422199) and the PHOEBE phase 3 (NCT03080805) studies, patients were randomized to receive pyrotinib plus capecitabine or lapatinib plus capecitabine. In the PHENIX phase 3 (NCT02973737) study, patients were randomly assigned and given pyrotinib plus capecitabine or placebo plus capecitabine. Patients who had received neither anti-HER2 agents nor chemotherapy for the relapsed or metastatic disease were included in the analyses, and the pooled tumor response data (per blinded independent central review) were reported herein. Results: In the pooled analysis of all three studies, 145 patients received pyrotinib plus capecitabine. The median progression free survival (PFS) was 12.4 months (95% CI, 11.1 months to not reached). The objective response rate (ORR) reached 72.4% (95% CI, 64.4% to 79.5%). In the pooled analysis involving the phase 2 and PHOEBE phase 3, 84 patients were treated with pyrotinib plus capecitabine and 62 patients with lapatinib plus capecitabine. The PFS was significantly prolonged with pyrotinib plus capecitabine vs lapatinib plus capecitabine (median, 12.4 months [95% CI, 11.1 months to not reached] vs 8.2 months [95% CI, 5.5 to 9.7 months]; hazard ratio, 0.40 [95% CI, 0.25 to 0.66]; p = 0.0001). The ORR was 71.4% (95% CI, 60.5% to 80.8%) with pyrotinib plus capecitabine compared with 58.1% (95% CI, 44.8% to 70.5%) with lapatinib plus capecitabine. Conclusions: The pooled analysis demonstrated pyrotinib plus capecitabine was efficacious as first-line therapy in patients with HER2-positive relapsed or metastatic breast cancer, offering a potent treatment option for these patients.
A national real-world prospective study to assess the effectiveness of adjuvant trastuzumab-dkst in HER2 breast cancer.
Authors: Alves Leandro Ladislau , Facó Lara Lopes , Cardoso Ana Carolina , Alcantara Alexandre , Figueiredo Augusto Theodoro , Rodrigues Rafaella , Gandufe Fatima , Silva Fernanda Cristina , Castilho Vivienne Carduz 
Published: May 2020

e13023 Background: Real-World Evidence (RWE) are gain importance once they are designed to evaluate the effectiveness of drugs whose efficacy has already been demonstrated in randomized controlled trials. In 2017, Brazil approved the first biosimilar of trastuzumab for treatment of breast cancer (BC) with overexpression of HER2. The anti-HER2 treatment significantly improves outcome in patients with HER2-positive BC. Trastuzumab-dkst is clinically effective biosimilar and help to increase access to BC treatment. The aim of this RWE is to address the effectiveness of adjuvant biosimilar trastuzumab-dkst in Brazilian women with early HER2+ BC. Methods: This is a national, multicenter, observational, prospective, RWE study conducted in Brazilian institutions. A hundred and seventy female adult patients, with diagnosis of early stage HER2-positive BC, who received at least one dose of trastuzumab-dkst as adjuvant therapy will be included. The follow-up period will be 5 years after the first dose of trastuzumab-dkst, unless tumor recurrence or death. The safety endpoints are the occurrence adverse events. The effectiveness endpoints are invasive disease relapse-free survival rate at 18, 24, 30 and 36 months after the start of biosimilar use, the invasive disease relapse-free survival after curative-intent surgery and overall survival after curative intent surgery. Given the inexistence of a specific hypothesis to be tested, sample size was based on the accuracy of the two-sided 95% confidence interval (95% CI) for the invasive disease relapse-free survival rate. Results: The recruitment planning covered 21 sites across the five regions of Brazil: North, Northeast, Midwest, Southeast, and South. From those 21 sites, 14 ( > 50%) have already been approved by their local ethical committee for patient recruitment. At 7 months, we have enrolled 50 patients over the five Brazilian regions, which means 29.4% of the total. Conclusions: To conduct RWE in Brazil is still challenging and we have listed 5 possible reasons: (1) there are few RWE studies running in the country, (2) we do not have trialists experienced in RWE design; (3) low medical commitment to adverse event report in RWE; (4) low budget for RWE; (5) slow ethics and regulatory process approval in Brazil. Considering the pioneering and challenges to develop the RWE in Brazil, we are achieving optimum adherence from medical sites. Moreover, roughly one quarter of the target recruitment was reached in the first 7 months after the study start date. Clinical trial information: NCT03892655 .
Real-world clinical outcomes in patients receiving cyclin-dependent kinase 4/6 inhibitors (iCDK 4/6) for hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer in Mexico.
Authors: Rodriguez Benigno , López Zepeda Lorena , Noguez-Ramos Alejandro , Vazquez Juarez Daniela , Camacho Limas Christian Patricio , Regalado Porras Gabriela Olivia , Salcedo Ivonne , Rivera Samuel , Aguayo Alvaro , Blanco Vazquez Yazmin Carolina , Lopez Galindo Angel Azael , Shveid Gerson Daniela , Perez-Zincer Fernando , Serrano Juan Alberto , Martínez-Herrera José Fabián , Olivares Guillermo , Villalobos Alberto , Gonzalez De Leon Cesar , Gerson Raquel 
Published: May 2020

e13053 Background: Breast cancer was the second most common malignant tumor diagnosed in 2018 worldwide, and the main cause of cancer death in women. In Mexico is the leading cause of cancer deaths, the most common molecular subtypes is HR+/HER2- (63%). The addition of iCDK 4/6 can enhance the benefit seen with endocrine therapy (ET) alone. In this work we will describe the experience in a “real world” model, of two tertiary-level hospitals in Mexico, with the use of iCDK 4/6 in a period of 3 years. Methods: Retrospective review of medical records of all consecutive pts with histological diagnosis of metastatic breast cancer HR+/HER2- and iCDK 4/6 treatment at our Institutions from July 2016 to January 2019. Clinical and pathological variables at diagnosis were recorded. Progression free survival was estimated using Kaplan-Meier method and survival distributions were compared using the Log-rank test. To assess association variables and progression we use Chi square. Results: 65 pts were treated, all with iCDK 4/6 in combination with ET, either aromatase inhibitor or irreversible estrogen receptor antagonist. 62 with palbociclib and 3 with ribociclib; Median age was 53 y/o (IQR 42-63), ECOG 0-1 (92.3%), 80% was metastatic recurrent disease, 92% of these patients received endocrine adjuvant treatment. Median estrogen receptor percentage was 90 (IQR 61-92), progesterone 50 (9-83), KI67 20 (10-30). The metastatic sites were bone (64.6%), liver (41.5%), nodal (33.8%), lung (21.5%), CNS (3.1%) and others (18.5%). 26 pts (40%) received iCDK 4/6 in the first line, 21 (32.3%) in the second line, and 27% in subsequent lines. Any grade of toxicity was presented in 44 pts (67.7%), Most common toxicities were neutropenia (63%), fatigue (16.9%), anemia (9.2%), grade 3-4 toxicities were presented in 21.5% and 17 pts (26.2%) required any dose adjustment. At the cut-off date, 28 pts (43.1%) had disease progression, median time to progression for the 65 pts was 10 months (1-84). OR for first line treatment vs subsequent lines was 0.14 (0.04-0.47, 95%, p = 0.001). OR for pulmonary metastases were 4.21 (1.15-15.31, 95%, p = 0.03), for other sites of metastasis were NS. Conclusions: Our outcomes suggest that the PFS is better when iCDK 4/6 are used as a first line treatment. Pulmonary metastases are may associated with poorly outcomes. In low- and middle-income countries, efforts should be focused on early therapy with iCDK 4/6.
Retrospective analysis of ribociclib and letrozole as first-line therapy in patients with hormone receptor (HR) positive metastatic breast cancer (MBC) within a managed access program (MAP) in Turkey.
Authors: Basaran Gul , Demirci Umut , Yildiz Fatih , Cicin Irfan , Aktas Burak Yasin , Ozturk Banu , Sezgin Goksu Sema , Coskun Hasan Senol , Oyan Basak , Sonmez Ozlem , Eralp Yesim , Gokmen Erhan , Gunduz Seyda , Korkmaz Taner , Sendur Mehmet Ali Nahit , Keskin Serkan 
Published: May 2020

e13055 Background: The combination of ribociclib with ET significantly increased progression free survival (PFS) and OS compared with ET in first line treatment of HR positive HER2 negative MBC. We aimed to evaluate the efficacy and safety of ribociclib and letrozole within Turkish MAP in order to present clinical outcome with the real-world use of ribociclib, outside of clinical trial setting. Methods: Turkish MAP enabled access to ribociclib in combination with letrozole as first-line therapy for MBC patients with HR positive and Her-2 negative tumors. Adequate bone marrow reserve, a normal QTc interval, normal renal and liver functions were required for eligibility. Patients received 600 mg ribociclib once daily for 3 wks followed by 1wk off. A retrospective chart review of patient demographics, clinical and treatment characteristics have been performed. Results: Between July and November 2017, 178 patients were included from 47 institutions in Turkey. We report the results of first 101 patients analyzed. The median age was 53 years (33–81 years) and median follow up was 16 months. Forty-six patients had de novo disease, 78% patients were postmenopausal, 22% had ovarian function suppression. Thirty-six % patients had adjuvant chemotherapy, 49% received adjuvant ET. Forty % had visceral disease. Thirty patients had grade 3 neutropenia, 3 patients had febrile neutropenia, 5 patients have grade 2-3 elevation of liver function tests. There was no QT prolongation. Dose reduction to 400 mg was required for 16 patients. Four patients discontinued ribociclib due to toxicity, 22 patients due to progression, one patient refused treatment. Twelve patients had complete remission as their best response. Median PFS was 24.12 months (95%CI 22.2-26.2). None of the clinical and pathologic factors were significantly associated with prolonged PFS. Conclusions: The efficacy and toxicity of first-line ribociclib and letrozole within Turkish MAP is similar to the results from randomized clinical studies for patients with HR positive, Her-2 negative MBC.
Prescribing preferences for hormone sensitive (HR+) metastatic breast cancer (mBC) in the CDK 4/6 inhibitor (CDK 4/6i) era.
Authors: Feinberg Bruce A. , Wojtynek Jeffrey , Dokubo Igoni , Jeune-Smith Yolaine , Kish Jonathan , Gajra Ajeet 
Published: May 2020

e13058 Background: CDK 4/6i is a category 1 guideline-recommended therapy for HR+/HER2- mBC in both first-line (1L) with an aromatase inhibitor and second-line (2L) with fulvestrant and without prior CDK 4/6i. We sought to understand community oncologists’ (c-oncs) prescribing preferences and sequencing for 1L, 2L, and third-line (3L) HR+/HER2- mBC patients across several common clinical scenarios (CS). Methods: C-oncs were presented 4 hypothetical HR+/HER2- mBC clinical scenarios (CS 1-4) via web-based survey. CS differed by menopausal status, prior adjuvant therapy and nature of metastases (mets) (i.e., bulky liver, lung, bone), but otherwise uniform: asymptomatic presentation, PI3K negative, identical response extent and duration in 1L, 2L, and 3L. Treatment preferences: hormonal (H), single agent (SA) or combination chemotherapy (CC) for 1L, 2L, and 3L in each CS were queried. We describe these preference patterns. Results: 47 U.S. c-oncs participated: mean years in practice was 22.7 and mean mBC patients under active treatment was 23.3. Preference for treatment and sequence, regardless of CS, per LOT were: 1L = 71% H, 14% SA, 16% CC; 2L = 51% H, 31% SA, 16% CC; and 3L = 35% H, 59% SA, 6% CC (Table). Of the 71% who preferred 1L H, the CDK4/6i % were: 73% overall, 58% when mets described as bulky liver, 94% when described as bone and or lung. The preference for pre-planned sequential chemo-hormonal therapy in 1L resulted in 63% of initial chemotherapy followed immediately by H; of which CDK 4/6i was preferred in 47%. In total, the initial and post-chemo CDK4/6i 1L preference was 80%. 2L hormonal preferences by frequency were: everolimus + exemestane = 38%, CDK 4/6i + fulvestrant = 20%, fulvestrant = 19%. SA preferences: 2L = capecitabine 46%, taxane 25%; 3L = capecitabine 40%, eribulin 32%. CC preferences included atezolizumab + nab-paclitaxel 24% in 1L and 16% in 2L. Conclusions: 1L HR+/HER2- mBC treatment is highly variable and preferences that warrant further research include: the role of CC, specifically atezolizumab + nab-paclitaxel; repeated CDK4/6i line of therapy; H therapy post CDK4/6i progression; and optimal SA sequencing. [Table: see text]
A novel proteomic mass spectrometry-based approach to reveal functionally heterogeneous tumor clones in breast cancer metastases and identify clone-specific drug targets.
Authors: Hajjaji Nawale , Abbouchi Mira , Nguyen Lan Anh , Charles Samuel , Leclercq Sarah , Bertin Delphine , Robin Yves-Marie , Fournier Isabelle , Salzet Michel 
Published: May 2020

e13063 Background: Breast cancer mortality is expected to rise by almost 30% by 2030 worldwide, mainly due to the occurrence of distant metastases. The development of drugs specifically targeted at tumor drivers has not yet curbed resistance to treatment, which prevents metastases curability. There is a need for new molecular approaches to tackle metastases complex biology, particularly tumor heterogeneity, a main determinant of resistance. The aim of this study was to use a proteomic mass spectrometry-based approach to reveal functionally heterogeneous’ tumor subpopulations in breast cancer metastases, and identify clone specific drug targets. Methods: Metastasis biopsies (n = 21) were collected retrospectively from patients with advanced breast cancer treated at Oscar Lambret Cancer Center (Lille, France). Tumor heterogeneity was analyzed directly on FFPE tissue sections using MALDI mass spectrometry imaging (MSI) on a RapifleX Tissuetyper. Unsupervised spatial segmentation was performed to reveal tumor subpopulations with distinct proteomic profiles within each metastasis. The full proteomic characterization of these tumor clones was further performed with spatially resolved proteomic mass spectrometry. Results: MSI revealed that breast cancer metastases contained 2 to 5 functionally distinct tumor clones (proteomic clones). Although the clone profiles within a metastasis were correlated, unsupervised hierarchical clustering showed a clear distinction between them and specific proteomic signatures. Enrichment analysis showed that differentially expressed proteins were involved in a variety of biological processes or pathways including regulation of histone acetylation, extracellular matrix degradation, DNA repair, NOTCH pathway, estrogen-responsive target genes or exocytosis. The evolution of the proteomic clones profile during disease progression was also determined by comparison of paired biopsies. To identify the candidate treatments best fitted to metastasis heterogeneity, the specific proteomic signatures of the clones were matched against a druggable genome database. It was possible to unveil candidate drug targets personalized to each metastasis functional clone. Conclusions: MALDI mass spectrometry imaging combined with spatially resolved proteomics has the potential to tackle breast cancer metastases heterogeneity, and identify candidate drug targets specific to functional clones to personalize treatments.
Yttrium-90 radioembolization for breast cancer with liver metastases: A focus on mortality, adverse reactions, and radiological response.
Authors: Heckman Patrick , Martinez Brandon , Birhiray Ruemu E. 
Published: May 2020

e13065 Background: Breast cancer associated with liver metastases (BCLM) occurs later in the progression of metastatic breast cancer and carries a poorer prognosis than bone or soft tissue metastases (Pagani). As systemic therapy begins to prolong progression, there is an inherent necessity for localized therapy directed at distant metastases. Further, there is some evidence to suggest that interventional techniques can prolong survival and palliate symptoms although data is lacking in this area (Hoe). Here we present findings describing the mortality benefit, adverse effects, and radiological response to Yttrium-90 (Y-90) radioembolization in BCLM patients. Methods: All patients with BCLM who received Y-90 radioembolization at St. Vincent Hospital from 2013-2018 were included in data collection. Digital chart review was utilized for data collection. To be eligible for the study, patients must have image or biopsy proven metastatic breast cancer to the liver, active unresectable disease not appropriate for ablation, ECOG performance status of 0-2, Bilirubin < 2.0 mg/dL, and no other evidence of liver disease. Patients with a life expectancy less than 2 months were excluded. Results: Twenty-five patients with BCLM underwent Y-90 radioembolization of hepatic metastases. Median survival after therapy was 495 days, or 16 months compared to the median survival rate of 4 months for BCLM patients reported by previous studies (Hoe). At 3 month follow up CT, 48% of patients experienced significant reduction in hepatic tumor burden, only 20% had worsening disease. 16% of patients reported abdominal pain. Median increase in bilirubin was 0.1. Median post procedural AST was 47, and ALT 40. Six patients experienced ascites requiring paracentesis, which occurred on average 14.3 months after Y-90 therapy. There were zero cases of pancreatitis and Radioembolization Induced Liver Disease (REILD). Conclusions: In patients with BCLM who undergo Y-90 radioembolization there seems to be a mortality benefit compared to traditional therapies. Further, there is a radiological reduction in tumor burden, and only minimal adverse effects.