tbuckley/cabot-search huggingface dataset:
Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer
Authors: A. Bardia, S.M. Tolaney, K. Punie, D. Loirat, M. Oliveira, K. Kalinsky, A. Zelnak, P. Aftimos, F. Dalenc, S. Sardesai, E. Hamilton, P. Sharma, S. Recalde, E.C. Gil, T. Traina, J. O’Shaughnessy, J. Cortes, M. Tsai, L. Vahdat, V. Diéras, L.A. Carey, H.S. Rugo, D.M. Goldenberg, Q. Hong, M. Olivo, L.M. Itri, S.A. Hurvitz
Journal: Annals of Oncology (2021)

The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes.Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline.Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations.SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.
The positive impact of mentoring on burnout: Organizational research and best practice interventions for cancer hospital employees.
Authors: Katelyn Cavanaugh, Bret Belfer, Debbie Cline, Courtney Holladay, Todd Alan Pickard, Evan Thoman, Shine Chang
Journal: Journal of Clinical Oncology (2021)

11012 Background: While burnout is not a new concept, combating it is becoming an increasingly important focus for organizations across all industries. Recently, the World Health Organization recognized burnout as an “occupational phenomenon” (WHO, 2019), and it was included in the 11th Revision of the International Classification of Diseases, where it is defined as “a syndrome conceptualized as resulting from chronic workplace stress that has not been successfully managed.” The University of Texas MD Anderson Cancer Center addresses burnout at the institutional level in support of all 22,000 workforce members. One avenue of this work focuses on mentoring. Mentorship, both formal and informal, has demonstrated positive effects to include empirical investigations that demonstrate its benefit in reducing risk of burnout in multiple settings for a variety of audiences (Qian et al., 2014; Thomas &amp; Lankau, 2009; van Emmerik, 2004; Varghese at al., 2020). Although mentoring is not as flashy as other interventions, what the last year has shown is that people need human connection now more than ever. Methods: In order to investigate the relationship between burnout and mentoring in our organization, we analyzed responses to our biennial voluntary employee survey, in which all employees were asked whether they are involved in a mentoring relationship and completed a single-item burnout scale. Results: We analyzed the survey data using a chi-square test and found that employees participating in mentoring relationships were less likely to report burnout than employees who are not participating in a mentoring relationship, χ2 (1, 14,486) = 17.431, p &lt; 0.005. The same pattern held for all types of employees; faculty, classified staff, leaders, clinical employees, and non-clinical employees, indicating that the experience of mentorship may be universal regardless of role, rank, and type of work. We suspect that the benefits of mentoring are bi-directional for mentors and mentees, though this should be investigated directly. Conclusions: Both formal and informal types of mentoring programs exist within MD Anderson to support retention, professional fulfillment, and reduce burnout. All employees have access to a centralized online mentoring platform to find a mentor. Formal mentoring support is also provided through various programs developed for specific professional cohorts, including physicians, advanced practice providers, and registered nurses. In addition, informal mentoring support is offered in the form of employee volunteer wellness champions. Together, these formal and informal mentoring programs have positively influenced burnout across the organization.[Table: see text]
Antifungal imidazole: Potential new antineoplastic agent-cytotoxic effects on non-small cell lung cancer cell lines (A549).
Authors: Erkan Kahraman, Erdem Goker
Journal: Journal of Clinical Oncology (2021)

e21037 Background: There are many drugs that can be applied to the treatment of lung cancer. These therapeutics include classical chemotherapeutics, targeted drugs against driver mutations, and immunotherapeutics. However, still, new agents are required to better results and patients outcomes. Recently, imidazole and its compounds, a type of antifungal drugs, were found to have antitumor efficacy in several cancer types. Its effects on non-small-cell lung cancer cells are yet known. This study aimed to detect anti-cancer properties of imidazole on non-small-cell lung cancer cells and suitability for clinical usage as an anti-cancer agent. Methods: We used A549 cell lines that are non-small-cell lung cancer cells in this study. A549 cells were treated with imidazole (molecular grade) at 1, 5, 10, 20, 40, 80 mM doses for 24, 48 and 72 hours. Cytotoxicity and IC50 values (the half-maximal inhibitory concentration) were calculated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis. Colony formation assay was performed to detect the effect of imidazole on cancer cell colony formation ability. The cellular morphological alterations were observed on bright-field microscopy using Giemsa staining. Cellular migration status of A549 cells was defined with in vitro scratch assay up to 48th hour. Results: Cytotoxicity assay results showed that low-level imidazole induced cell proliferation. However, high-level imidazole treatment decreased the cell viability of A549 cells in a dose and time-dependent manner. The IC50 value was calculated as 60 mM, 28 mM, and 15,9 µM doses respectively at 24, 48, 72 hours in A549 cells. Also, we determined that the number of colonies (number of colonies: 42.7 ± 3.06) formed in A549 cell lines treated with imidazole at IC50 dose was statistically less than the colony number of the control group (number of colonies: 70.7 ± 5.13) (p &lt; 0.01). Interestingly, we observed that colony number increased at a low dose (at 5 mM) imidazole treated group, statistically significant (p &lt; 0.05). Cellular morphology was not affected at low doses; however, at the IC50 dose, A549 cells changed their cellular morphology, lost cell-cell contact, decreased cytoplasmic volume, and differentiated from parental morphology. In addition to these effects, we observed that imidazole treated cells decreased their migration capabilities compared with control group cells (p &lt; 0.05). Conclusions: Our results have shown that antifungal imidazole treatment inhibits cancer cell biological responses such as proliferation, colony formation ability, and motility in non-small lung cancer cell lines in a dose and time-dependent manner. These results suggest that imidazole would be the right candidate for the synergy with other therapeutic options such as immunotherapy. This introductory study allows us further studies exploring the synergy and its mechanism.
East Kent trust is fined £733 000 for unsafe care of mother and baby
Authors: Clare Dyer
Journal: BMJ (2021)

A hospital trust that admitted failing to provide safe care and treatment for a newborn baby and his mother has been ordered to pay a fine of £733 000.

East Kent Hospitals University NHS Foundation Trust pleaded guilty last April to providing unsafe care resulting in avoidable harm to Harry Richford and his mother, Sarah, in the first such criminal prosecution of an acute care NHS trust.1 At a sentencing hearing on 18 June at Folkestone magistrates court the trust was fined £733 000 and ordered to pay a £170 victim surcharge and prosecution costs of £28 000. …
Racial and ethnic disparities among participants in precision oncology clinical studies.
Authors: Christopher M. Aldrighetti, Andrzej Niemierko, Eliezer Mendel Van Allen, Henning Willers, Sophia C. Kamran
Journal: Journal of Clinical Oncology (2021)

3014 Background: Precision medicine has revolutionized oncologic care in the United States (US) in the past two decades. While the US cancer population is rapidly diversifying, enrollment of a diverse patient population into clinical trials lags behind. In particular, it is unclear whether minority patients are adequately represented in precision oncology trials. Herein, we report racial/ethnic representation in precision oncology studies spanning four common cancer types (breast, lung, prostate, colorectal cancers). Methods: Completed US clinical studies incorporating precision medicine objectives based on a set of 12 precision oncology search terms (including tumor biomarker, whole exome sequencing, tumor mutation testing, gene expression signatures, tumor microarray, tumor genomics, et cetera) were identified from Clinicaltrials.gov. Studies were reviewed for reporting race/ethnicity for inclusion in the analysis. The Surveillance, Epidemiology, and End Results (SEER) database was used to determine incidence of race/ethnicity in the US cancer population, correlated with disease site and median year of enrollment for each trial. The difference in incidence (D-I) was defined as the median absolute difference in study racial enrollment and SEER incidence, with a negative value corresponding to underrepresentation. Wilcoxon signed-rank test was used to compare median D-I to a value of 0 by racial/ethnic subgroups. Results: Overall, 156 studies were identified; 40.3 and 27.5% studies enrolling from 2000 through 2020 met the inclusion criteria for racial and ethnic subgroups reporting, respectively. Of 4,418 total enrollees, 82.5% were White, 10.5% Black, 3.8% Asian, and 0.4% American Indian/Alaskan Native (AIAN). Ethnically, 6.4% were Hispanic. The D-I was +2.2% for Whites (interquartile range (IQR) = -43.7% to 25.4%; P &lt; 0.013), -0.74% AIAN (IQR = -0.8% to +5.9%; P &lt; 0.001), -2.5% Asians (IQR = -4.1% to 30.4%; P &lt; 0.152), -4.6% Blacks (IQR = -20.1% to +45.0%; P &lt; 0.001), and -8.1% Hispanics (IQR = -14.8% to + 29.6%; P &lt; 0.001). By disease site, Blacks were significantly underrepresented proportional to their cancer incidence among prostate (D-I of -11.8%, p = 0.009) and lung studies (D-I of -5.9%, p = 0.013), while prostate studies significantly overrepresented Whites (D-I +14.0%, p = 0.005). Lung studies overrepresented Asians (D-I +0.49%) consistent with the prominent role of targetable oncogene drivers in this population. Conclusions: Results demonstrate an underrepresentation of minority racial groups and an overrepresentation of Whites in precision oncology studies. Increased emphasis on equitable enrollment onto these studies is critical, as resulting precision Omic conclusions are used to stratify populations and personalize treatments. A continued lack of diversity among enrollees may further leave behind vulnerable minority populations in the era of precision oncology.
Abstract 17175: Trendsin Alcoholic Cardiomyopathy Hospitalizations and In-Hospital Mortality and Comorbidity. United States, 2005-2014
Authors: Samian Sulaiman, Arshad Jahangir, Vijayadershan Muppidi, Addis Asfaw, Muhammad Shahreyar, Nazdar Yousef, Romina Wingert
Journal: Circulation (2018)

Background: Yearly trends and prevalence of alcoholic cardiomyopathy (ACMP) hospitalizations and its associated in-hospital mortality, arrhythmia, complications and outcomes are not well studied on a national level. Methods: We used Nationwide Inpatient Sample database (2005-14) and identified 25402 hospitalizations for adults (≥18 yrs) with a primary or secondary diagnosis of ACMP . Since ACMP is a diagnosis of exclusion, all patients with a co-diagnosis of CAD or other causes of cardiomyopathy were excluded. Results: Taking the growth of the US general population into account, there was a decreasing number of ACMP hospital stays per 100,000 persons (4.38 in 2005 vs 3.62 in 2014; p &lt; 0.001). Arrhythmias were present in in 48.7% of hospital stays. In-hospital mortality was 4.2% down-trending over years (4.3% 2005 vs 3.7% 2014) but this was not statistically significant (p = 0.78). Approximately 2.1% experienced cardiac arrest(uptrend from 1.4% to 3.2% in 2005-14; p &lt;0.001). Prevalence of arrhythmia in this population has increased from 2005 to 2014 (46.5% vs 51.6%; p &lt;0.001). Mean age was 55.01 ±12.2 yrs and 85.2% were male. Patients with arrhythmia were older (57.08 vs 53.03; p&lt;0.01), had more comorbidities (Elixhauser index 2.55 vs 1.85; p &lt; .01). Gender and racial differences were noted between arrhythmia and non-arrhythmia group respectively: Male (88.6% vs 82%; p&lt; 0.01),White (68.2% vs 57.4%), Black (18.8% vs 28.5%) (p &lt; 0.01) . AFib was the most common type of arrhythmia (30.7%), followed by V Tach (8.7%), unspecified arrhythmia (8.6%), and AFlutter (5.6%). Median charge per hospital stay was $25909. Median length of stay was 4 d. Despite that the Median length of stay (4 days) has not changed (4 days in 2005 vs 5 days in 2014; p = 16%), Median charge per hospital stay has increased from $18223.5 to $34056 : p &lt;0.01. Cardioversion was performed in 1.2 %, Catheter ablation in 0.4 %, PPM implantation in 0.7 %, ICD in 1.5 %, cardiac catheterization in 16 % and VAD in 0.1% of hospitalizations for alcoholic cardiomyopathy. Utilization of these procedures has increased from 12% in 2005 to 14.6% in 2014 (p = 2.6%) Conclusion: There was a decreasing number of ACMP hospitalizations per 100,000 of US population. Despite the increased prevalence of arrhythmias in this population over years, the in-hospital mortality has not change, but rate of cardiac arrest has increased. The Median length of hospital stay has not changed, but the healthcare cost has significantly increased. This could be explained by the increased utilization of inpatient cardiac procedures.
Angiopoietin-2 early increase to predict benefit from regorafenib in metastatic colorectal cancer (mCRC) patients: The prospective REGOLAND study.
Authors: Federica Marmorino, Carlotta Antoniotti, Alessandra Boccaccino, Maria Antista, Nadia Zaffaroni, Gemma Zucchelli, Antonia Martinetti, Elisa Campi, Daniele Rossini, Elisa Sottotetti, Beatrice Borelli, Francesca Corti, Veronica Conca, Roberto Moretto, Marco Maria Germani, Alfredo Falcone, Mirella Giordano, Gianluca Masi, Filippo Pietrantonio, Chiara Cremolini
Journal: Journal of Clinical Oncology (2021)

e15566 Background: Regorafenib is a treatment option for refractory mCRC patients with no validated predictors of benefit. We previously showed that, among several circulating angiogenic factors, low baseline Ang-2 and Tie-2 plasma levels were associated with good prognosis and that the early increase of Ang-2 during the treatment could predict benefit from regorafenib ( Antoniotti et al, J Clin Oncol 36:675-675, 2018). To prospectively validate these retrospective findings, we conducted the REGOLAND study. Methods: Ang-2 and Tie-2 were assessed by ELISA on plasma samples collected at baseline (d1) and after 15 days (d15) of treatment in a cohort of mCRC patients receiving regorafenib, as per indication. To detect a HR for PFS of 0.50 in favour of the early increase (Δd15-d1) of Ang-2 levels, setting two-sided α = 0.05 and β = 0.10, 87 events were required according to Schoenfeld design. Comparisons among concentrations of each marker at d1 and d15 were performed by Wilcoxon test. Median values at baseline were used as cut-off to discriminate patients with low versus high plasma levels and their correlation with outcome was analysed. Results: One hundred patients were included. Median PFS and OS were 2.5 and 6.7 months, respectively. The early increase of Ang-2 at d15 was reported in 42 patients and was associated with longer PFS (median 2.7 vs 2.4 months; HR for PFS: 0.72 [95%CI:0.48-1.08], P = 0.095). As compared to d1, an overall decrease of Tie-2 levels at d15 was observed ( P = 0.007), but it was not associated with clinical outcome. Low levels of Ang-2 at baseline were associated with longer PFS (HR: 0.59 [95%CI:0.39-0.89], P = 0.005) and OS (HR:0.62 [95%CI:0.41-0.94], P = 0.017), while Tie-2 levels were not. In the multivariate model, the association of Ang-2 levels with PFS was confirmed (HR:0.48 [95%CI:0.31-0.76], P = 0.001), but not with OS (HR: 0.80 [95%CI:0.49-1.28], P = 0.351). Conclusions: Ang-2 is a prognostic marker and its early modulation predicts clinical benefit among mCRC patients treated with regorafenib. We hypothesize that Ang-2 levels early increase as a consequence of the successful inhibition of Tie-2 by regorafenib that leads to a compensatory increase of the ligand and correlates with anti-tumour activity.
Stereotactic body radiation therapy and in situ oncolytic virus therapy followed by immunotherapy in metastatic non-small cell lung cancer.
Authors: Carlo Guerrero, Joe E. Ensor, Kai Sun, Andrew M. Farach, Sindhu Nair, Jun Zhang, Monisha Singh, Jorge German Darcourt, Priya V. Ramshesh, Edward Brian Butler, Bin S. Teh, Mark Sultenfuss, Nakul Gupta, Helen E. Heslop, Jaime A. Mejia, Jenny Chee Ning Chang, Eric Bernicker
Journal: Journal of Clinical Oncology (2021)

9115 Background: The introduction of immunotherapy has altered the treatment paradigm for metastatic non-small cell cancer (mNSCLC). Unfortunately, many patients with mNSCLC have limited or no benefit from immune checkpoint inhibitors (ICIs). A variety of approaches have been explored to augment the efficacy of ICIs. Our study’s aim was to determine whether the addition of stereotactic body radiation therapy (SBRT) and intratumoral injection of the oncolytic virus ADV/HSV-tk (adenovirus-mediated expression of herpes simplex virus thymidine kinase) to a monoclonal antibody targeting programmed cell death-1 (PD-1) would improve the ICI’s efficacy in the treatment of mNSCLC. Methods: In this single-arm, open-label phase II study, patients with mNSCLC (squamous or non-squamous) who were ICI-naive or who were previously treated with a maximum of one line of therapy that included an ICI received an intratumoral injection of ADV/HSV-tk (5 x 10 11 vp) followed by SBRT (30 Gy in 5 fractions) to the same tumor. An anti-PD-1 agent (pembrolizumab 200 mg IV every 3 weeks or nivolumab 240 mg IV every 2 weeks) was then given for up to 24 months (pembrolizumab) or 12 months (nivolumab), or until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A secondary endpoint was clinical benefit rate (CBR). Results: A total of 35 patients were enrolled, with 28 (80%) receiving pembrolizumab and 7 (20%) receiving nivolumab; 14 (40%) had previous ICI therapy while 21 (60%) were ICI-naive. The ORR and CBR were 28.5% and 61.9% in the ICI-naive group, and 14.2% and 64.2% in the group that previously received an ICI, respectively. Grade 3 or higher toxicity was seen in five patients (26.3%) in the ICI-naive group and in one patient (7.1%) in the previously ICI-treated group. No treatment-related deaths were observed. Conclusions: The addition of SBRT and intratumor injection of ADV/HSV-tk to anti-PD-1 therapy in mNSCLC resulted in a CBR of over 60% for both ICI-naive and previously ICI-treated patients without the use of chemotherapy. The combination was able to reinstitute sensitivity to ICIs in patients previously treated with an ICI, and also benefited some patients whose tumors did not express PD-L1. These findings should be further explored in a larger study population. Clinical trial information: NCT03004183. [Table: see text]
“Arrogant” surgeon who put his initials on patients’ livers can practise again
Authors: Clare Dyer
Journal: BMJ (2021)

A consultant surgeon who was convicted of assault for branding his initials on the livers of two anaesthetised transplant patients has been allowed to practise again after convincing a tribunal that he was no longer the “arrogant surgeon” he was at the time.

Simon Bramhall admitted assault and was fined £10 000 at Birmingham Crown Court in 2018, in a case described by prosecutors as “without precedent in criminal law.”1

Last December a medical practitioners tribunal suspended him from the medical register for five months. A review tribunal on 4 June decided that he was fit to practise again after remedying his misconduct …
Abstract 12958: Comparison of INR Values Between Self- and Telemedicine-Managed Anti-Coagulation in LVAD Patients
Authors: Elisa Vogeler, Maja Theresa Dieterlen, Jens Garbade, Sven Lehmann, Julia Fischer, Khalil Jawad, Alaeldin Addas, Michael Borger, Anna Meyer
Journal: Circulation (2018)

Introduction: Exact monitoring of therapeutic-range International Normalized Ratio (INR) after left ventricular assist device (LVAD) implantation is an important aim to reduce the risk of thrombosi...