bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular circular RNAs to promote the growth and metastasis of triple-negative breast cancer through remodeling the tumor immune microenvironment.
Authors: Yang Sujin , Tang Jinhai 
Published: June 2021

e13047 Background: Triple-negative breast cancer (TNBC) has been confirmed to have a high degree of heterogeneity of breast cancer, which is more common in young women, with a high degree of malignancy, lack of effective clinical treatment and poor prognosis. Recently, many studies have also found that immune microenvironment (IME) can remarkablely affect the occurrence and metastasis of TNBC through exosome-mediated molecular transmission. Therefore, there is an urgent need to find new immune-related molecules as therapeutic targets and to predict the progress of TNBC and prognosis of treatment. Methods: Using RNA-sequencing and bioinformatics analysis, we found the differential-expressed circular RNAs (circRNAs) in exosomes from TNBC cell lines (BT549 and MDA-MB-231), non-TNBC cell lines (MCF-7 and MCF-10A) and tissues from breast cancer patients. Then, we used CIBERSORT and ESTIMATE algorithm to explore the tumor-infiltrating immune cells (TICs) or stromal components in IME, and identified the significant differential-expressed mRNAs in the immune cells between TNBC and non-TNBC samples. RT-qPCR was used to confirm the expression level of selected circRNAs and mRNAs in TNBC cell lines. Results: We profiled the circRNAs in the exosomes from TNBC cell lines and breast cancer patients by RNA sequencing and detected 27 significantly differentially-expressed circRNAs. After bioinformatic analysis and RT-qPCR, circRELB and circANXA1 were chose to further study. TICs and IME scores were found to associated with the survival and clinicopathological characteristics of TNBC patients and IME remodeling. Interestingly, 92 differentially-expressed genes were found to be enriched in the NF-kB signaling pathway and mTOR signaling pathway. Moreover, we identified 33 target genes of circRELB and circANXA1 by cross-analysis. Based on the predicted miRNAs and the corresponding mRNAs and circRNAs, we have established an IME-related circRNA-miRNA-mRNA network. Then, Kaplan-Meier plots showed the expression levels of certain targeted genes (PTEN, CCND1, IL6, CDKN1A, AKT1, TNF and WNT1) were connected to prognosis in TNBC metastasis patients. Conclusions: The expression levels of circRELB and circANXA1 was found significantly upregulated in exosomes from TNBC cell lines and tumor tissues from breast cancer patients. In addition, circRELB and circANXA1could affect the expression of downstream target genes by competing for endogenous RNA (ceRNAs), and ultimately promote the metastasis of TNBC and remodeling of IME. In summary, this study analyzes the mechanisms of exosome-contained circRNAs in TNBC and these targets from the IME-related circRNA-miRNA-mRNA network may be new potential prognostic biomarkers and immune treatment strategies to prevent the development and metastasis of TNBC.
Real-world clinical effectiveness of eribulin in metastatic breast cancer patients with visceral metastases in the United States.
Authors: Mougalian Sarah Schellhorn , Zhang Jingchuan , Kish Jonathan , Zettler Marjorie E. , Feinberg Bruce A. 
Published: June 2021

e13058 Background: Eribulin mesylate was approved in the United States (US) in 2010 for the treatment of metastatic breast cancer (mBC) after at least two prior chemotherapeutic regimens, which should have included an anthracycline and a taxane in either the adjuvant or metastatic setting. Visceral metastases, including those to the lung and brain, have been identified as poor prognostic features for patients with mBC. The objective of this analysis was to assess the real-world clinical effectiveness of eribulin in mBC patients with visceral metastases when treated in accordance with the US label. Methods: Patients with mBC initiating eribulin consistent with the US label between 2011-2017 were identified through a retrospective, multi-site chart review study conducted in US oncology practices. De-identified, patient-level demographics, clinical characteristics, treatment patterns, and outcomes were entered into an electronic case report form by the patients’ treating physicians. Sites of metastases at initiation of eribulin were indicated by providers. Clinical outcomes assessed included best overall response to eribulin as recorded in the patient’s chart, progression-free survival (PFS), and overall survival (OS). The proportion of patients with either a complete or partial response as their best overall response was calculated. PFS and OS were calculated by the Kaplan-Meier method from the initiation of eribulin for all patients with visceral metastases and subsets reporting lung or brain metastases site, respectively. Results: The analysis included 470 patients with visceral metastases, including 342 with lung metastases and 22 with brain metastases at the time of eribulin initiation. Eribulin was third-line therapy for approximately three quarters of patients in these subgroups, and the remainder received eribulin in fourth line or later. Mean age was 59 years in general (59 and 54 years in those with lung and brain metastases, respectively). Over half of patients (53.6%) had either a complete or partial response to eribulin. Median PFS was estimated at 6.0 months, and median OS was estimated at 10.5 months. Results for the subgroups of patients with lung and brain metastases are shown in the table. Conclusions: The results of this retrospective analysis affirm clinical effectiveness of eribulin in mBC patients with visceral metastases, when used consistent with the US label.[Table: see text]
The prognostic value of cytoskeletal regulation and vesicle trafficking signaling pathway mutation in breast cancer.
Authors: Liu Haiyan , Huang Guanqun , Huang Tanxiao , Liu Ming , Liao Wenting , Yang Bo , Liu Yuanyuan , Chen Shifu 
Published: June 2021

e13068 Background: Breast cancer (BC) is the most commonly diagnosed cancer in 2020, with an estimated 2.3 million new cases and the leading cause of cancer death in women. The cytoskeleton is a dynamic system of protein filaments that is regulated by dozens of proteins which are, in turn, regulated by phosphoinositides. Cytoskeletal regulation and vesicle trafficking (CRVT) signaling pathway is associated with many changes in the structure and movements of cells. Few studies addressing the association between genetic mutation of the CRVT pathway and the disease prognosis have been reported up to now. Here we investigate the genetic status of CRVT pathway as a biomarker for predicting overall survival (OS) and relapse-free survival (RFS) for breast cancer patients. Methods: We used cBioPortal platform to analyze a cohort of 10646 breast cancer samples. Mutations in 7 genes ( APC, BAP1, KEAP1, PAK1, PTEN, SRC, STAT3 ) are the most common indication in the CRVT signaling pathway. We define overall survival (OS) as the time between the procedure date when the tumor specimen was collected and the date of death or last follow-up visit. And we define relapse-free survival (RFS) as the time from surgical resection to relapse of disease. We estimated and compared the survival curves of these two groups using Kaplan-Meier method and log-rank tests. The statistical significance level was set to 5% ( p < 0.05). Results: Genomic alterations of the CRVT-indicator genes were found in 2582 (n = 2582/10646, 24.25%) samples with sorts of alterations identified including variants of non-synonymous mutations, splicing mutations, short in-frame insertion and deletion, short frame shift insertion and deletion, and copy number gain and loss. PTEN was most commonly altered (n = 2329), followed by PAK1 (n = 863), APC (n = 718), STAT3 (n = 341), KEAP1 (n = 317), BAP1(n = 292), and SRC (n = 278). Based on the result, patients were divided into the CRVT and non-CRVT group. The median OS of the CRVT group was 141.57 moth, which was significantly shorter than the OS of the non-CRVT group (log-rank test p= 0.000662). The median RFS of the CRVT group was 167.76 moth, which was also significantly shorter than the RFS of the non-CRVT group (log-rank test p= 0.0169). Conclusions: To the best of our knowledge, this study is the first investigation to evaluate the prognostic value of CRVT pathway mutation in patients with breast cancer. Our investigation shows that CRVT pathway mutation could significantly predict poor prognosis in breast cancer patients. The result of our analysis should be better confirmed with additional relevant research in the future using updated analyses.
Team huddle, education and infection screening as effective tools in continuing cancer care delivery during the peak of COVID-19 pandemic in 2020 in the Bronx, NY: Experience from a public teaching hospital.
Authors: Pathak Surabhi , Narurkar Roshni , Hasan Khan Mohammed , Jiang Bei , Soe May Nyein Chann , Muppidi Monica , Hwang Caroline 
Published: June 2021

e13500 Background: COVID-19 pandemic has affected healthcare delivery, particularly in the hard-hit areas. During the peak of COVID-19 pandemic crisis in the New York city, our outpatient oncology infusion center, located within a public teaching hospital in the South Bronx remained active. We implemented twice daily team huddle, staff and patient education, and infection screening tools and modified treatment plans based on social, personal and disease related factors. We evaluate the effectiveness of the above strategies in timely delivery of critical oncological care. Methods: Patients treated from the March 1, 2020 to the May 8, 2020 were included. De-identified data from medical charts were analyzed using IBM SPSS Version 27.0. Bivariate logistic regression analysis was applied to identify factors associated with COVID-19. Results: In total, 170 patients were treated in 576 visits. Median age was 60.7 years, 44% Hispanic and 41% Black, median Charlson Comorbidity index (CCI) was 6.6. Fifty percent received cytotoxic chemotherapy, 44% targeted therapies and the remaining received immune-checkpoint inhibitors. Of the 170 patients, six developed severe COVID-19 requiring hospitalization. Their median age was 63 years with average of 10.5 days from infusion center visit to COVID-19 and median CCI score was 9, higher than the rest of the cohort. Two patients died, 3 made complete recovery, 1 enrolled in hospice. Two patients contracted mild COVID-19 managed in the outpatient setting. Diabetes mellitus was associated with severe COVID-19 [OR: 25.9 (95%CI: 1.3-519, p=0.03)]. Age, gender, type of cancer and oncological treatment, smoking, CCI, growth factor support, nursing home residence, statin use were not associated with risk of developing severe COVID-19 Conclusions: Cancer treatment in the outpatient setting using an approach focused on careful patient selection, infection prevention strategies and strong team communication is feasible and allows for continuity of critical oncological care. Receipt of cancer directed therapy was not associated with higher risk for infection compared to risks associated with community-based transmission.. In communities with high community-based transmission, careful selection of patients for oncological based treatment is paramount.
Impact of primary care providers (PCPs) on care receipt and satisfaction in adolescent and young adult (AYA) oncology patients.
Authors: Hess Eric , Parkes Amanda Marie 
Published: June 2021

e13512 Background: While there has been ongoing work to define the role of primary care providers (PCPs) in adolescent and young adult (AYA) survivorship models, little has been done to understand the role of PCPs earlier in the care continuum. As PCP-shared models of care have been theorized to help address morbidity related to the physical and psychosocial effects of cancer and its treatment, there is a need to better understand the impact of PCPs on AYAs. Given this, we sought to study the influence of PCPs in the care of AYAs with cancer, comparing care receipt and satisfaction during treatment versus in survivorship. Methods: Electronic health record query identified adult AYA cancer patients 19-39 years with at least two visits at the University of Wisconsin from 3/30/2019-3/29/2020. Identified patients were sent an electronic survey to assess care team members and impact on care. Responses were categorized based on patient-reported presence of a PCP as part of their cancer care team. For the data analysis, all patients who did not self-identify as long-term survivors, defined as 5+ years since diagnosis, were defined as active patients. Given survey answers were not mandated for all questions, the denominator was unique for each question. Results: We found a minority of AYAs responding to our survey considered a PCP as part of their cancer care team (71/173, 41%). PCP presence led to improved satisfaction in all AYAs with addressing the impact of diagnosis/treatment on peer interactions and independence, with 67% (45/67) AYAs with a PCP very or some satisfied versus 55% (53/97) without a PCP. PCPs also decreased the likelihood that supportive care services weren’t received by patients due to a lack of knowledge of the services, seen in 64% (56/88) AYAs without a PCP versus 52% (32/62) with a PCP. As seen in table, there were several findings suggesting that PCP involvement in AYA care was more critical to active patients than long-term survivors, including supportive care service receipt and satisfaction with such services. Conclusions: Overall, we found PCP involvement on cancer care teams was important for AYAs defined as both active patients and long-term survivors. Despite this, less than half of all patients identified PCPs as part of their care team. Our data suggest PCP-shared models of cancer care may improve care utilization and satisfaction in AYAs and support efforts to incorporate PCPs as meaningful members of the care team throughout all phases of care. Survey responses based on PCP inclusion as cancer care team member and patient treatment status.[Table: see text]
Multi-site practice and physician travel burden by oncology specialty.
Authors: Frosch Zachary AK , Hicks-Courant Katherine , Bekelman Justin E. , Ko Emily Meichun , Kanter Genevieve P. 
Published: June 2021

e13513 Background: Having physicians who practice at multiple sites may increase patients’ access to care, but also burden physicians Gynecologic oncologists (GO) are increasingly practicing at more sites across a larger geographic area, but the degree to which medical oncologists (MO), surgical oncologists (SO) or radiation oncologists (RO) are also doing so is unknown. Methods: We conducted a retrospective, observational study using data from the 2020 Physician Compare National Dataset. We included GO, MO, SO, RO, as determined by self-reported specialty. Practice sites with incomplete street addresses were excluded. For each specialty, we calculated the number of practice sites per physician, geographic practice dispersion (median driving distance required to go to each practice site), and temporal practice dispersion (median travel time required to go to each practice site). We used linear regression to compare the number of practice sites, geographic practice dispersion, and temporal practice dispersion by specialty. Results: The number of physicians, mean number of practice sites, along with geographic and temporal practice dispersion by specialty are shown in the table. MO practiced at a smaller number of practice sites compared to GO (p<0.001) and RO (p<0.001). Compared to MO, SO had a smaller geographic dispersion (median driving distance 22 miles vs. 38 miles, p=<0.001) and temporal practice dispersion (median driving time 27 minutes vs. 43 minutes, p<0.001), whereas RO had a larger geographic dispersion (median RO driving distance 58 minutes, p<0.001) and temporal practice dispersion (median RO driving time 63 minutes, p<0.001). Conclusions: Oncologic specialties vary in the number of practice sites and practice dispersion per oncologist. In particular, GO and RO practice at more sites than MO, with MO practices more geographically concentrated than RO practices. While SO practice at a similar number of practice sites compared to MO, their practices are the most geographically concentrated. While these practice patterns may represent increased patient access to specialty oncology care, the impact on quality of care and physician wellness is unknown.[Table: see text]
The impact of COVID-19 on oncologists: Experience from Egyptian physicians.
Authors: Omar Abeid Mohamed Athman , Ramadan Marwa , Khamis Yomna , Ismail Abdelsalam A. 
Published: June 2021

e13514 Background: The unprecedented emergence of coronavirus disease (COVID-19) has disrupted the patients' and physicians' daily activities, including cancer care. However, little is known on how COVID-19 has impacted oncologists from low and middle-income countries. Methods: We conducted a cross-sectional survey among eighty-eight practicing oncologists in Alexandria governorate, Egypt. An electronic, anonymized self-reporting survey was distributed in February 2020 to collect information on occupational safety measures, the prevalence of COVID-19 among respondents, workload, and family support during the pandemic Results: Out of 88 contacted oncologists, 75% completed the survey (n=66). Nearly half (45%) of respondents were residents, 36% were specialists, and 18% were consultants. The mean age of respondents was 34.79 years (SD ±10.42). More than half of the respondents were not comfortable managing cancer patients during the pandemic (56%) and did not feel well-protected at the workplace (58%). However, most (79%) had managed a cancer patient with COVID-19 more than once. Furthermore, almost all participants (98%) have worked with an infected colleague. Nevertheless, to more than half (54%), it made no difference working with a colleague who was previously infected. Most physicians (79%) felt overwhelmed with workload than the pre-pandemic period. Despite being COVID-19 negative, nearly half reported their family members had reduced contact with them due to the fear of being infected. In contrast, 24% are now getting more family support, whereas 27% are experiencing the same contact level as before the COVID-19 era. Physicians lacking family support had a significantly higher burnout rate than those who had family support (p=0.038). However, the burnout rate was similar regardless of doctors' rank, or treating COVID-19 patients, or feeling protected at work. The majority of the participants (75%) had experienced COVID-19 like symptoms, and one third (n=21) were confirmed COVID-19 infected: residents - 52%, specialists - 33%, and consultants - 14%. Nevertheless, we found no association between the rank and being infected with COVID-19 (p=0.632). Most participants thought they were infected at the hospital (38% by patients; 24% by colleagues), and 14% by family members. However, there was no significant association between being infected and feeling protected at work (p=0.823). Most of the infected physicians (61%) received moral support from both the family and colleagues, and 33% received family support only. There was no association between burnout rate and being COVID-19 infected (p=0.719). Conclusions: One-third of the oncologists were COVID-19 positive. Besides, most oncologists feel overwhelmed with workload and experience more burnout than before the COVID-19 era, and it worsens if one lacks family support.
Efficacy of a clinical risk prediction tool to prioritize outreach for high-risk cancer patients.
Authors: Croyle Megan , Handley Nathan , Li Michael , Binder Adam F , Csik Valerie Pracilio 
Published: June 2021

e13524 Background: Acute care utilization (ACU), including emergency department visits and hospitalizations, is common in patients with cancer. Prospectively identifying patients’ risk status may enable interventions to reduce ACU. We developed a REDUCE score (Reducing ED Utilization in the Cancer Experience for active oncology patients (defined as patients with an active cancer diagnosis in the last 12 months who had a Medical Oncology encounter in a 180-day period) to prospectively determine risk of ACU. The intended intervention was outreach to all high-risk patients. We evaluated the high risk group over an 11-month period (February through December 2020) to better characterize those who received outreach. Methods: Analysis of high-risk patients was conducted using a case-control method over two periods: February through June 2020 (Period 1) and July through December 2020 (Period 2) to account for a change in the type of outreach deployed. High risk was defined as REDUCE ≥2. High risk scores were stratified by those with REDUCE =2 and those with REDUCE >2. Control Group 1 consisted of high-risk patients with REDUCE =2 who did not receive outreach, and Control Group 2 included high-risk patients with REDUCE >2 who did not receive outreach. Case Group 1 consisted of high-risk patients with REDUCE =2 who had outreach, and Case Group 2 included patients with REDUCE >2 who had outreach. Average ACU per patient was compared across all groups over both periods. Descriptive statistics were applied. Results: Results are described in table 1. Average ACU per patient was higher in Periods 1 and 2 for both Case Groups, compared to both Control Groups. Over time, there was a trend in decreased ACU in the intervention group with stable to increasing ACU in the control groups. The proportion of patients who received outreach across both periods decreased in Case Group 1, but increased in Case Group 2. Conclusions: These findings suggest that patients who received outreach were at a higher risk of ACU. Further investigation revealed that there was not consistent prioritization of patients with the highest risk scores within the high-risk group for outreach. In addition to the REDUCE , ongoing efforts incorporate clinical judgment of the outreach team in assessing additional clinical risk factors to determine an intervention, which is meaningful. The REDUCE tool may provide value as an initial screening mechanism. Average ACU per patient by study group.[Table: see text]