bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of early progression (EP) to CDKIs first line treatment in ER+/HER2- metastatic breast cancer (MBC) using machine learning.
Authors: Jerez Jose Manuel , Ribelles Nuria , Rodriguez-Brazzarola Pablo , Diaz Redondo Tamara , Jimenez Rodriguez Begoña , Sanchez-Muñoz Alfonso , Marquez Antonia , Carabantes Francisco , Pajares Bella , Villar Ester , Bermejo-Perez Maria-Jose , Saez Lara Enrique , Dominguez-Recio Maria Emilia , Godoy Ana , Mesa Hector , Galvez Carvajal Laura , Franco Leo , Ruíz Sofía , López Irene , Alba Emilio 
Published: May 2020

e13040 Background: The treatment of luminal MBC has undergone a substantial change with the use of cyclin dependent kinase 4/6 inhibitors (CDKIs). Nevertheless, there is not a clearly defined subgroup of patients who do not initially respond to CDKIs and show EP. Methods: MBC ER+/HER2- patients who have received at least one line of treatment were eligible. The event of interest was disease progression within 6 months of first line treatment according to the type of therapy administered. The first line treatments were categorized in chemotherapy (CT), hormonal therapy (HT), CT plus maintenance HT and HT plus CDKIs. Free text data from clinical visits registered in our Electronic Health Record were obtained until the date of first treatment in order to generate a feature vector composed of the word frequencies for each visit of every patient. Six different machine learning algorithms were evaluated to predict the event of interest and to obtain the risk of EP for every type of therapy. Area under the ROC curve (AUC), True Positive Rate (TPR) and True Negative Rate (TNR) were assessed using 10-fold cross validation. Results: 610 RE+/HER2- MBC treated between November 1991 and August 2019 were included. Median follow up for metastatic disease was 28 months. 17426 clinical visits were analyzed (per patient: range 1-173; median 30). 119 patients received CT as first line treatment, 311 HT, 117 CT plus maintenance HT and 63 HT plus CDKIs. There were 379 patients with disease progression, from which 126 were within 6 months from first line treatment (54 events with CT, 57 with HT, 4 with CT plus maintenance HT and 11 with HT plus CDKIs). The model that yields the best results was the GLMBoost algorithm: AUC 0.72 (95%CI 0.67-0.77), TPR 70.85% (95%CI 70.63%-71.06%), TNR 66.27% (95% 66.08%-66.46%). Conclusions: Our model based on unstructured data from real-world patients predicts EP and establishes the risk for each of the different types of treatment for MBC ER+/HER2-. Obviously an additional validation is needed, but a tool with these characteristics could help to select the best available treatment when that decision has to be made, avoiding those therapies that are probably not to be effective.
Radiomics risk score (RRS) on CT to predict survival and response to CDK 4/6 inhibitors in hormone receptor (HR) positive metastatic breast cancer (MBC).
Authors: Kunte Siddharth , Braman Nathaniel , Bera Kaustav , Leo Patrick , Abraham Jame , Montero Alberto J. , Madabhushi Anant 
Published: May 2020

e13041 Background: The addition of CDK 4/6 inhibitors (CDK) to endocrine therapy (ET) is the standard of care for HR+ MBC. Currently, no robust predictive markers for CDK inhibitors exist. We hypothesized that baseline imaging features on pre-treatment CT scans using machine learning could correctly identify responders to CDK. Methods: From a retrospective pt registry, 46 pts with HR+ MBC who received palbociclib (palbo) plus ET and had liver metastases were identified, and divided at random into equally sized training and testing cohorts. Patients with objective response/stable disease per RECIST v1.1 were defined as ‘responders’ (65%), and those with progressive disease within 6 months were ‘non-responders’ (35%). The median age at diagnosis was 62. All pts were ER+ and 4% were HER2+. 65% pts received palbo as 1st or 2nd line tx. 503 radiomic texture features measuring subtle differences in lesion heterogeneity on a pixel level were extracted on pre-treatment CT within the first lesion measured for RECIST assessment. An elastic net Cox proportional hazards model was constructed within the training set to derive a Radiomics Risk Score (RRS), which was evaluated for association with prognosis and response within the testing set. A risk score threshold was chosen in the training set for stratifying patients into high and low risk groups. Results: The RRS consisted of 4 radiomic features indicating intratumoral heterogeneity to be associated with poor outcome. In the independent testing set (n = 23), RRS was continuously associated with survival (p = .0027) on multivariate analysis, along with age and RECIST response (Table). Categorical risk groups were similarly associated with survival in the testing set (p = .00491, HR = 4.03, CI = 0.6772). Median survival time in low and high risk groups were 2.33 and 0.673 years, respectively. When compared against RECIST response in the testing set, RRS was found to also be predictive of response with an ROC curve of 0.675. Conclusions: Radiomics analysis was able to predict response and survival in HR+ MBC pts prior to initiation of treatment with CDK. [Table: see text]
Keeping oncologists current with CDK4/6 inhibitors in HR+ breast cancer: The impact of online education.
Authors: Parikh Kinjal , Tanzola Mindy , Peters Pamela M. , Cristofanilli Massimo 
Published: May 2020

e13044 Background: CDK4/6 inhibitors have revolutionized the care of patients with hormone receptor positive (HR+), HER2-negative breast cancer, improving survival outcomes. There are multiple CDK4/6 inhibitors available that differ in their pharmacologic features, reported outcomes, therapeutic indications, and adverse event profiles. Education is needed to empower clinicians to optimally use these agents in practice and personalize breast cancer treatment. The goal of this educational initiative was to increase the knowledge, competence, and confidence of oncologists regarding clinical trial data and factors for selection of CDK4/6 inhibitor. Methods: This educational approach included a 30-minute online video discussion among 3 expert faculty, synchronized with slides to support the discussion. Educational effectiveness was assessed with repeated paired pre/post assessment in which learners served as their own controls. A chi-square test assessed differences from pre- to post-assessment. P values < .05 are statistically significant. Effect size was calculated using Cramer’s V test by determining the strength of the association between CME and the outcomes (V = .16-.26 is considerable and V > .26 is extensive). The activity launched 11/25/2019 and data are reported through 2/4/2020. Results: A total of 889 learners, including 513 physician learners, participated in the activity from 11/2019 through 2/2020. Participation in the education resulted in significant improvements in knowledge among oncologists (n = 81; p < .001; V = 0.16). On average, the proportion of learners who responded correctly to knowledge-based questions about CDK4/6 inhibitors increased from 51% at the pre-assessment to 67% at the post-assessment. Moreover, 41% of oncologists had a measurable positive change in confidence in their ability to incorporate CDK4/6 inhibitors into the treatment of HR+, HER2- advanced breast cancer. Significant improvements in knowledge were observed in the following areas: The clinical trial safety and efficacy data evaluating CDK4/6 inhibitors in the management of patients with HR+/HER2-negative breast cancer (32% vs. 51%, p < .05, V = 0.19). The potential role of patient- and tumor- specific prognostic factors in selection of individual CDK4/6 inhibitors (56% vs. 72%, p < .05, V = 0.17). Conclusions: This CME-certified online discussion resulted in statistically significant gains in oncologists’ knowledge and improved confidence surrounding the personalization of CDK4/6 inhibitor therapy in HR+/HER2- breast cancer.
Comparison of treatment-related adverse events (TRAE) of different CDK4/6 inhibitors (CDK4/6i) in metastatic breast cancer (MBC): A network meta-analysis.
Authors: Desnoyers Alexandra , Nadler Michelle , Kumar Vikaash , Saleh Ramy , Amir Eitan 
Published: May 2020

e13052 Background: CDK4/6i in combination with endocrine therapy (ET) are a standard of care in hormone receptor positive, HER2 negative MBC. Palbociclib, ribociclib and abemaciclib have all been approved and while efficacy appears similar, differences in safety and tolerability are apparent. Here we quantify TRAEs comparing the 3 CDK4/6i in a network meta-analysis. Methods: We searched PubMed and ASCO and ESMO proceedings to identify randomized trials (RCT) of CDK4/6i. Data on common and serious TRAE were extracted for each approved CDK4/6i. The odd ratio (OR) for each TRAE and the hazard ratio (HR) for progression-free survival (PFS) were calculated relative to ET alone. A network meta-analysis was then performed for each ET backbone (aromatase inhibitor (AI) or fulvestrant) to compare ribociclib and abemaciclib to palbociclib. Results: 7 RCT were included in the analysis and comprised 2715 patients receiving CDK4/6i (palbociclib: 789 patients; ribociclib: 1153 patients; abemaciclib: 773 patients). In 4 RCT (1440 patients) ET backbone was an AI and in 3 RCT (1275 patients) it was fulvestrant. Compared to palbociclib, ribociclib and abemaciclib showed lower grade 3-4 hematological toxicity, but higher GI toxicity (see table). Treatment discontinuation was higher with abemaciclib than other CDK4/6i. Efficacy of the 3 CDK4/6i was similar. Compared to palbociclib, for AI backbone, the HR for PFS for ribociclib was 1.00 and for abemaciclib 1.04. For fulvestrant backbone, the HR were 0.88 and 0.93 respectively. Conclusions: The three approved CDK4/6i show comparable efficacy, but differences in safety and tolerability. Abemaciclib has worse tolerability with significantly higher treatment discontinuation likely due to gastro-intestinal toxicity. [Table: see text]
Real-world survival data of palbociclib in advanced and metastatic breast cancer: A multicenter experience in Lebanon.
Authors: Nasr Lewis , Ghoche Ahmad , Diab Saada , Nasr Fadi 
Published: May 2020

e13054 Background: Approximately 70% of all breast cancer cases are hormone receptor (HR) positive. One of the most important treatment strategies for HR positive, human epidermal growth factor receptor 2 (HER2) negative subtype was endocrine treatment monotherapy by targeting estrogen receptor or aromatization and thus reducing estrogen level. However, resistance to this treatment and disease progression is universal. In the past few years, palbociclib, an oral inhibitor of cyclin dependent kinase 4 and 6 have been approved by the FDA, as a new standard of care in the metastatic or locally advanced setting either as front line therapy or after progression. The aim of our study is to describe the real world experience with palbociclib. Methods: Eligible patients had histologically confirmed metastatic breast cancer estrogen and progesterone receptors positive and HER2 receptor negative. Palbociclib was given 125 mg orally for 21 consecutive days of a 28 day cycle. Patients were followed over one year. Primary objective was progression free survival (PFS). Tumor response and treatment tolerability were defined as secondary objectives. Results: From 2002 to 2018, we identified a total of 44 breast cancer patients. All patients were females. The median age at diagnosis was 57 years. Among all the patients, 33.3% had visceral metastasis, 35.9% had non visceral metastasis and 30.8% had the two types of metastasis. 64.1% were de novo metastatic and 35.9% were not de novo metastatic. 82.5% had less than 3 sites of metastasis. 47% of the study patients had received both chemotherapy and endocrine therapy during treatment course, and 13 % had only received prior adjuvant endocrine therapy. 28.26% took only prior systemic therapy for breast cancer. By the cutoff date for the final analysis (1/11/2018), a total of 8 events of disease progression occurred, no death events happened. The median progression free survival was 262.6 months for palbociclib combined with letrozole as first line. Conclusions: no data was published before on palbociclib in Lebanon. We are the first to describe these characteristics. Our result (PFS 26 2.6 months) is in conformity with the PFS obtain with PALOMA-2 (24 months).
EARLY real-world treatment and dosing patterns of ribociclib for metastatic breast cancer (mBC): A retrospective observational study.
Authors: Balu Sanjeev , O'Shaughnessy Joyce , Paul Mary Lisha , Baidoo Bismark , Sudharshan Lavanya 
Published: May 2020

e13059 Background: Ribociclib and abemaciclib in combination with endocrine therapy have demonstrated survival benefit in women with HR-positive/HER2-negative mBC. This study assessed early real-world treatment and dosing patterns of ribociclib for mBC in a US community oncology setting. Methods: This was a retrospective, observational, descriptive study of female mBC patients initiating treatment with ribociclib between March 1, 2017 and September 30, 2018 within the US Oncology Network (USON) and followed through December 31, 2018. USON’s iKnowMed (iKM) EHR database was used to identify patients and medical chart data review was conducted to abstract treatment information. Descriptive analyses were performed to assess patient and treatment characteristics. Results: A total of 161 patients were selected for chart review, of which 116 patients who received ribociclib were confirmed as eligible. The mean age of patients at initiation of treatment was 66 (SD 14) years. Among patients with documented menopausal status, 90% were post-menopausal, and 10% were pre-menopausal. Among patients with documented receptor status, 99% were ER+/HER2-. Patients most commonly initiated ribociclib in the first-line setting (1L n = 52, 2L n = 30, 3L n = 9, 4L+ n = 25) and in combination with letrozole (n = 33, 28.4%). Eastern Cooperative Oncology Group (ECOG) performance score at time of ribociclib initiation was 0-1 in 60.4% of patients. Documented metastatic sites were present in bone (35.3%), lung (8.6%), and liver (6%). The most common comorbidities documented within 6 months of treatment initiation were cardiovascular disease (53.4%), diabetes (19%), and depression (18.1%). Overall, 46.6% (n = 54) of patients received prior neoadjuvant or adjuvant chemotherapy and 32.8% patients (n = 38) received prior neoadjuvant or adjuvant endocrine therapy. 95% of patients started at the full dose of 600mg. One-fourth of patients (n = 29) had a dose-hold and 27.6% (n = 32) patients experienced a dose reduction with ribociclib therapy. Conclusions: This study represents early ribociclib uptake in a real-world setting in the US. Early utilization demonstrates patients receiving ribociclib are older and sicker than those in pivotal clinical trials. Substantial heterogeneity in ribociclib initiation by LOT was observed.
Ixabepilone efficacy and tolerability in metastatic breast cancer (MBC) patients in a real-world setting.
Authors: Hyder Tara , Rosenzweig Margaret Q. , Brufsky Adam 
Published: May 2020

e13067 Background: Ixabepilone is a microtubule stabilizing agent that was approved as monotherapy and in combination with capecitabine for the treatment of refractory metastatic or locally advanced breast cancer. With limited options for refractory MBC, especially in triple negative breast cancer (TNBC), ixabepilone has demonstrated an increase in progression free survival (PFS) in randomized control trials. We assess the effectiveness and safety of the drug in a real-world setting. Methods: A large, ongoing clinical database of over 1800 women (1999 to present) was used to identify 91 patients who had received ixabepilone during their treatment course. Clinical outcomes were retrospectively analyzed utilizing descriptive and comparative statistics. Results: Treatment was late in the disease course; median line of treatment was 5.3. At the time of receiving ixabepilone, the patients PFS was 3.5 months with n = 4 patients attaining a PFS > 12 months. Overall survival (OS) was 11.3 months. A subset of patients that had triple negative breast cancer (N = 37) had similar PFS, 3.6 months, and OS, 10.2 months, as the total population. Most common adverse events of any grade were fatigue (37%), nausea (32%), and peripheral sensory neuropathy (28%). Grade 3 or higher anemia was present in 10% of the patients. Conclusions: Ixabepilone has demonstrated efficacy in the treatment of patients with MBC, including the challenging population of TNBC patients in this real-world example. It is also well tolerated. These findings make ixabepilone a reasonable chemotherapeutic agent for refractory MBC and TNBC patients. [Table: see text]
Development of an artificial intelligence model to dynamically predict metastatic recurrence of early-stage breast cancer patients.
Authors: Vaidya Vivek Prabhakar , Agrawal Smita , M Sai Vinod , Nagdewani Sandeep , Chandrashekaraiah Prajwal , Bhardwaj Tapasya , Narayanan Babu 
Published: May 2020

e13078 Background: Models that can dynamically predict risk of metastatic breast cancer (MBC) recurrence based on cumulative historical clinical data could help guide patient care & surveillance decisions. The objectives of this study were to predict risk of MBC recurrence dynamically from any point after 1 year of initial diagnosis in a BC patient’s journey. We show representative results for predicting 4 year risk post 1 year of date of diagnosis. There are established models to predict risk of distant recurrence at the time of diagnosis but we have not found much work on dynamic risk scores. Methods: We used a set of 3807 patients from the Concerto HealthAI database of oncology EMR data that includes clinical data from CancerLinQ Discovery to build this model that were further enriched by expert nurse curators. The average age at diagnosis was 58 & the average follow up period for this cohort of patients was 6.6 years. The cohort included patients of all breast cancer subtypes. 628 patients had metastatic recurrence within 4 years post 1 year of date of diagnosis. We used 60% of the data for training, 20% for hyper-parameter tuning & 20% for testing & tried out various machine learning (ML) algorithms including Linear Regression, Lasso, Random Forest, Extremely Random Forests, & XGBoost. Extremely Random Forest built using 330 features had the best performance. Results: The performance of various ML algorithms for predicting metastatic BC recurrence within 4 years post 1 year from date of diagnosis is provided in the table below with sensitivity held constant at 0.7. Key variables influencing the results in each model are also indicated. The Extremely Random Forest model for predicting risk of metastatic recurrence within 1 year from 1 year post diagnosis yielded an AUC of 0.814 & a balanced accuracy of 0.719. Conclusions: An AI model to predict risk of metastatic recurrence in breast cancer patients built using a real world dataset yielded promising results. Furthermore, analysis of input variables provided insights not only into the key features driving metastatic recurrence risk such as previous surgery, tumor subtype, stage & age at diagnosis etc. Such a model could be a useful for assessing patient risk & treatment options at various points in a breast cancer patients journey as well as stratify patients for different levels of surveillance. [Table: see text]
Prognosis of breast cancer patients with initial bone metastasis: A population-based study.
Authors: LIU Deyue , Wu Jiayi , Zhu Li 
Published: May 2020

e13081 Background: Metastatic breast cancer (MBC) is a highly heterogeneous disease and bone is one of the most common metastatic sites. This retrospective study was conducted to investigate the clinical features, prognostic factors and benefits of surgery of breast cancer patients with initial bone metastases. Methods: From 2010 to 2015, 6860 breast cancer patients diagnosed with initial bone metastasis were analysed from Surveillance, Epidemiology, and End Results (SEER) database. Univariate and Multivariable analysis were used to identify prognostic factors. A nomogram was performed based on the factors selected from cox regression result. Survival curves were plotted according to different subtypes, metastatic burdens and risk group differentiated by nomogram. Results: Hormone receptor (HR) positive/human epidermal growth factor receptor 2 (HER2) positive patients showed the best outcome compared to other subtypes. Patients of younger age ( < 60 years old), white race, lower grade, lower T stage ( < = T2), not combining organ metastasistend to have better outcome. About 37% (2249) patients received surgery of primary tumor. Patients of all subtypes can benefit from surgery. Patients of bone-only metastases (BOM), bone and liver metastases, bone and lung metastases also showed superior survival time if surgery is performed. While patients of bone and brain patients cannot benefit from surgery (p = 0.05). The C-index of nomogram is 0.68. A cutoff value of nomogram point was identified by ROC curve as 93 points, which divided all patients into low-risk group and high-risk group. Patients of both groups showed better overall survival when receiving surgery. Conclusions: Our study has provided population-based nomogram in patients with initial bone metastatic breast cancer. The finding of potential benefit of surgery to overall survival will cast some light on the treatment tactics of this group of patients.
Feasibility of real-time serial comprehensive tumor analytics: Pilot study of olaparib and durvalumab in metastatic triple negative breast cancer (mTNBC).
Authors: Li Allen , Labrie Marilyne , Vuky Jacqueline , Lim Jeong Youn , Johnson Brett , Sivagnanam Sam , Betts Courtney , Coussens Lisa , Corless Christopher L. , Bergan Raymond C. , Gray Joe W. , Mills Gordon B. , Mitri Zahi Ibrahim 
Published: May 2020

e13092 Background: Longitudinal analysis of serial tumor biopsies is an under-utilized approach to studying adaptive mechanisms of resistance. We have established a comprehensive analytic platform to evaluate real-time trial sample analysis to inform precision oncology combinations in mTNBC. The primary endpoint of the study is feasibility of completing all CLIA assays within 28 days of biopsy. Methods: Following a pre-treatment biopsy and 4 weeks of olaparib monotherapy mTNBC patients underwent an on-treatment (tx) biopsy and durvalumab was added to their therapy. Pre- and on-tx biopsies underwent comparative analysis using CLIA assays (immunohistochemistry-IHC, whole exome seq, RNAseq and phospho-proteomics) as well as research assays (multiplex IHC-mIHC, cyclic immunofluorescence-IF, and reverse phase protein array-RPPA). Results: Serial biopsies were obtained from all 3 enrolled patients, and the primary endpoint was achieved for all patients (Table). Treatment was well tolerated, and 2 patients achieved clinical benefit > 6 months. In one patient with a prolonged CR ( > 18 months), the on-tx sample exhibited dramatic changes in protein network rewiring by protein data analysis (RPPA, cyclic-IF), and an increase in immune infiltrate by mIHC. Conclusions: This pilot confirmed the feasibility of rapid real-time analysis to inform treatment decisions. This led to the development and initiation of biomarker driven olaparib combination trials in mTNBC at our institution. Clinical trial information: NCT03544125 . [Table: see text]