tbuckley/cabot-search huggingface dataset:
Optimizing internal referrals within an academic breast oncology practice.
Authors: Jamie L Carroll, Stephanie L. Amundson, Tufia C. Haddad, Karthik Giridhar
Journal: Journal of Clinical Oncology (2020)

48 Background: Improving new patient access to medical oncology clinics is a priority. Unlike external referrals which undergo a review process, internal referrals (from any Mayo department or community-based, affiliated health system) are scheduled directly. At times, these internal referrals lack necessary clinical information, or may be more appropriate for electronic consultation (e-consult). This impacts the patient experience, provider satisfaction, and access to new patient visits. A pilot program was implemented in the Medical Oncology breast clinic to review new internal referrals prior to scheduling. Methods: In 2018, all internally referred patients to Medical Oncology breast clinic were reviewed by an advanced practice provider in breast oncology. Electronic medical records were reviewed to collect diagnosis, pathology, radiology information and treatment to date. Internal referrals were either accepted directly to medical oncology breast clinic, triaged to an internal medicine clinic for workup of a new breast mass, converted to an e-consult, or declined as no medical oncology need was identified. Results: 52 patients were referred internally to Medical Oncology breast clinic. Of these, 29 (55.8%) were accepted directly as new consultations, 8 (15.4%) were triaged to the Internal Medicine clinic, 6 (11.5%) were converted to e-consults, and 6 (11.5%) were declined as not requiring breast medical oncology input. Of the 8 patients that started in the IM clinic, 6 eventually required Medical Oncology breast clinic consults for invasive breast cancers. The most common e-consult was for extending adjuvant endocrine therapy (3/6). 1/6 e-consults required a follow up consultation. The most common reason for declining a consult was no diagnosis of an invasive breast cancer (4/6). A total of 16/52 referrals (30.2%) did not require a breast oncology new consultation. Conclusions: Review of internal referrals improved the efficiency of new breast cancer medical oncology consultations. This review process has been implemented across the entire Medical Oncology practice.
Prostate cancer and COVID-19: Impactof hormonal therapy on severe outcomes
Authors: Karine Tawagi, Jeff Burton, Diana Maslov, Michael Lunski, Marc Matrana, Daniel Johnson
Journal: Clinical Cancer Research (2020)

Background: Early reports on cancer patients infected with COVID-19 have suggested a high risk of hospitalizationand death compared to the general population  Limited data are available on outcomes in specific cancer types  Weaim to identify whether hormonal treatment impacts severe outcomes (rate of hospitalization, ICU admission, intubation, and death) in prostate cancer patients  Methods: We conducted a multicenter study in the state of Louisiana, throughout the Ochsner Health System, inboth tertiary and nontertiary centers  Patients must carry a diagnosis of prostate cancer and have a completedSARS-CoV-2 test between March 1st and April 30th, 2020  Chi-squared and Fisher's exact tests were performed tocompare the proportion of patients experiencing severe outcomes between treatment groups  Results: As of April 30, 2020, a total of 56 patients with prostate cancer who had a positive SARS-COV-2 test wereidentified  Median age 69, median BMI 28 8, 78 6% (n=44) black, 58 9% (n=33) current/former smokers, HTN, DM2, and CKD were the most common comorbidities, and 12 5% (n=7) of patients had stage IV disease  Of thesepatients, 26 8% (n=15) were on hormonal treatment (received within 90 days of COVID+ test)  In terms of severeoutcomes, 58 9% (n=33) of patients required hospitalization, 17 9% (n=10) required ICU admission with 14 3%(n=8) patients requiring intubation, and 23 2% (n=13) of patients died  There was no statistical difference in rate ofsevere outcomes (rate of hospitalization, ICU admission, intubation, and death) among prostate cancer patientsreceiving hormonal therapy vs  those receiving no hormonal therapy  Conclusion: With an ongoing global pandemic of COVID-19, it is important to identify characteristics leading toincreased risk of severe events in cohorts of cancer patients  This small cohort does not identify hormonal therapyas a risk factor for increased rate of severe outcomes in patients with prostate cancer  Further analyses describingimpact of specific hormonal regimens on risk of hospitalization and death will be completed by time of presentation
Major Variation across Local Transplant Centers in Probability of Kidney Transplant for Wait-Listed Patients
Authors: Kristen L. King, S. Ali Husain, Jesse D. Schold, Rachel E. Patzer, Peter P. Reese, Zhezhen Jin, Lloyd E. Ratner, David J. Cohen, Stephen O. Pastan, Sumit Mohan
Journal: Journal of the American Society of Nephrology (2020)

Geographic disparities in access to deceased donor kidney transplantation persist in the United States under the Kidney Allocation System (KAS) introduced in 2014, and the effect of transplant center practices on the probability of transplantation for wait-listed patients remains unclear.To compare probability of transplantation across centers nationally and within donation service areas (DSAs), we conducted a registry study that included all United States incident adult kidney transplant candidates wait listed in 2011 and 2015 (pre-KAS and post-KAS cohorts comprising 32,745 and 34,728 individuals, respectively). For each center, we calculated the probability of deceased donor kidney transplantation within 3 years of wait listing using competing risk regression, with living donor transplantation, death, and waiting list removal as competing events. We examined associations between center-level and DSA-level characteristics and the adjusted probability of transplant.Candidates received deceased donor kidney transplants within 3 years of wait listing more frequently post-KAS (22%) than pre-KAS (19%). Nationally, the probability of transplant varied 16-fold between centers, ranging from 4.0% to 64.2% in the post-KAS era. Within DSAs, we observed a median 2.3-fold variation between centers, with up to ten-fold and 57.4 percentage point differences. Probability of transplantation was correlated in the post-KAS cohort with center willingness to accept hard-to-place kidneys (r=0.55, P<0.001) and local organ supply (r=0.44, P<0.001).Large differences in the adjusted probability of deceased donor kidney transplantation persist under KAS, even between centers working with the same local organ supply. Probability of transplantation is significantly associated with organ offer acceptance patterns at transplant centers, underscoring the need for greater understanding of how centers make decisions about organs offered to wait-listed patients and how they relate to disparities in access to transplantation.
Covid-19 treatment candidate hydroxychloroquine impairs tumor response to anti-PD1
Authors: Simon Wabitsch, Jack C. McVey, Chi Ma, Benjamin Ruf, Laurence Diggs, Bernd Heinrich, Tim F. Greten
Journal: Clinical Cancer Research (2020)

Background and Aims: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a worldwidehealth crisis  As of now, only one treatment has been established for the coronavirus infection disease 2019 (Covid-19), which has disproportionally affected patients with comorbidities such as cancer  Hydroxychloroquine (HCQ) hasbeen studied as a potential treatment for Covid-19  Here we studied whether HCQ treatment could influence theeffect of immunotherapy against colorectal and liver cancer  Methods: In vitro studies were conducted to assess the effect of HCQ on lymphocyte activation and proliferation aswell as cell growth and antigen presentation  Mouse cell lines used included MC38, CT26, RIL-175, SB1, and LD1while human tumor cell lines used were TFK-1 and EGI-1  Mice bearing subcutaneous MC38, CT26, and RIL-175tumors were treated with HCQ, anti-PD1, or both  Tumor volume was measured over 19 days  Systemic and tumor-infiltrating immune cells were analyzed by flow cytometry  Results: HCQ treatment impairs T-cell production of TNF-α and IFNγ in vitro and in vivo  Whereas cell growth wasdecreased in all tumor cell lines, in vitro treatment of tumor cells with HCQ revealed an upregulation of MHC-1 inCT26, SB1, LD1, TFK-1, and EGI-1 but not in MC38 and RIL-175  HCQ treatment impaired response to anti-PD1treatment in all subcutaneous models  Compared to control, HCQ treatment led to increased tumor growth in MC38tumors  Flow cytometry analysis revealed an impaired activation of CD4+ T cells as well as tumor-infiltratingcytotoxic antigen-specific CD8+ T cells  Conclusion: This study shows that HCQ treatment can result in immunotherapy failure due to a systematicimmunosuppressive effect that overcomes the increased MHC expression on tumor cells
Venetoclax and ibrutinib for patients with relapsed/refractory chronic lymphocytic leukemia
Authors: Carsten U. Niemann, Mark-David Levin, Julie Dubois, Sabina Kersting, Lisbeth Enggaard, Gerrit J. Veldhuis, Rogier Mous, Clemens H. M. Mellink, Johan A. Dobber, Christian B. Poulsen, Henrik Frederiksen, Ann Janssens, Ida Schjødt, Ellen C. Dompeling, Juha Ranti, Mattias Mattsson, Mar Bellido, Hoa T. T. Tran, Kazem Nasserinejad, Arnon P. Kater
Journal: Blood (2020)
Transcriptional Subtypes Resolve Tumor Heterogeneity and Identify Vulnerabilities to MEK Inhibition in Lung Adenocarcinoma
Authors: Anneleen Daemen, Jonathan E. Cooper, Szymon Myrta, Matthew J. Wongchenko, Eva Lin, Jason E. Long, Oded Foreman, Zora Modrusan, Jarrod R. Tremayne, Cecile C. de la Cruz, Mark Merchant, Scott E. Martin, Yibing Yan, Melissa R. Junttila
Journal: Clinical Cancer Research (2020)

Lung adenocarcinomas comprise the largest fraction of non-small cell lung cancer, which is the leading cause of cancer-related deaths. Seventy-five percent of adenocarcinomas lack targeted therapies because of scarcity of druggable drivers. Here, we classified tumors on the basis of signaling similarities and discovered subgroups within this unmet patient population.We leveraged transcriptional data from >800 early- and advanced-stage patients.We identified three robust subtypes dubbed mucinous, proliferative, and mesenchymal with respective pathway phenotypes. These transcriptional states lack discrete and causative mutational etiology as evidenced by similarly distributed oncogenic drivers, including KRAS and EGFR. The subtypes capture heterogeneity even among tumors lacking known oncogenic drivers. Paired multi-regional intratumoral biopsies demonstrated unified subtypes despite divergently evolved prooncogenic mutations, indicating subtype stability during selective pressure. Heterogeneity among in vitro and in vivo preclinical models is expounded by the human lung adenocarcinoma subtypes and can be leveraged to discover subtype-specific vulnerabilities. As proof of concept, we identified differential subtype response to MEK pathway inhibition in a chemical library screen of 89 lung cancer cell lines, which reproduces across model systems and a clinical trial.Our findings support forward translational relevance of transcriptional subtypes, where further exploration therein may improve lung adenocarcinoma treatment.See related commentary by Skoulidis, p. 913.
Covid-19: Three tier alert system takes effect across England
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Liverpool and neighbouring local authorities will become the first area of England to have new restrictions imposed under the new three tiered risk system designed to stem rising covid-19 infections across England, the government has announced.

Liverpool itself had 609 cases per 100 000 population on 13 October, a 14.3% rise over the previous week. Neighbouring Knowsley, included in the measures that apply to the Liverpool City Region, which also includes Halton, Sefton, St Helens, and Wirral, had 669.5 cases per 100 000. Liverpool has the steepest increase in covid-19 admissions to hospital in England, and the highest number, with more than 250 patients in beds at Liverpool University Hospitals NHS Foundation Trust, around 15% of bed capacity.

In a memo seen by the Health Service Journal , Steve Warburton, chief executive of the trust, said that it was scaling back non-urgent operations to help cope with the surge.1 “We recognise that this will be distressing for patients whose elective care needs to be …
Mental Health Disorders Related to COVID-19–Related Deaths
Authors: Naomi M. Simon, Glenn N. Saxe, Charles R. Marmar
Journal: JAMA (2020)

Steven H. Woolf, MD, MPH; Derek A. Chapman, PhD; Roy T. Sabo, PhD; Daniel M. Weinberger, PhD; Latoya Hill, MPH; DaShaunda D. H. Taylor, MPH
Pilot randomized controlled trial (RCT) in women with non-small cell lung cancer (NSCLC) to assess the feasibility of delivering group-based psychosocial care via videoconference.
Authors: Kathrin Milbury, Hannah M Higgins, Aileen B. Chen, Mara Antonoff, Yisheng Li, Anne S. Tsao, Eduardo Bruera
Journal: Journal of Clinical Oncology (2020)

257 Background: Women with lung cancer are vulnerable to psychological distress and social isolation, which may be related to the smoking-related stigma of the disease. We developed a group-based psychosocial intervention seeking to address the specific needs of this understudied patient population. The goal of this pilot RCT was to examine the feasibility and acceptability of delivering group-based psychosocial care via videoconference (i.e., Zoom). Methods: Women with NSCLC within 3 months of diagnosis completed baseline measures of their computer literacy and were then randomized to a group-based psychosocial intervention receiving coping skill training or a group-based attention control (AC) arm receiving psychoeducation. Both arms involved five, 60 min. videoconference sessions (groups of 3-5 patients) that were led by a master-level counselor. Participants completed one Zoom “practice run” prior to starting the group sessions. After the last session, they rated the overall experience of the intervention delivery and the specific software. Results: Seventy patients (mean age = 66 yrs with 54% over age 65; 71% non-Hispanic White; 50% college educated; 75% advanced stage) consented (63% consent rate) and 65 were randomized (intervention: N = 33; AC: N = 32). At baseline, 47% indicated that they use a computer daily while 50% said they rarely or never use a computer. Attendance was high in both arms (means: intervention = 3.18; AC = 3.56 with 63% attended all sessions). Across arms, 89% preferred a group-delivery and 92% preferred online delivery. The majority used a smartphone or tablet to participate (72%). Regarding the Zoom software, 71% said it was easy to use, 65% of women would recommend it to others, and 41% felt comfortable with it after one use (but 26% said they felt never comfortable with it). Only 44% thought that the sessions via Zoom were the same as they would have been in-person. Conclusions: It seems to be feasible and acceptable to deliver group-based psychosocial interventions via videoconference in women with NSCLC undergoing treatment. Challenges regarding scheduling the group sessions and familiarizing infrequent computer users with the technology were encountered but were resolved over the course of the trial. Clinical trial information: NCT03731585 .
Effect of Germline Mutations in Homologous Recombination Repair Genes on Overall Survival of Patients with Pancreatic Adenocarcinoma
Authors: Siddhartha Yadav, Pashtoon M. Kasi, William R. Bamlet, Thanh P. Ho, Eric C. Polley, Chunling Hu, Steven N. Hart, Kari G. Rabe, Nicholas J. Boddicker, Rohan D. Gnanaolivu, Kun Y. Lee, Tricia H. Lindstrom, Gloria M. Petersen, Fergus J. Couch, Robert R. McWilliams
Journal: Clinical Cancer Research (2020)

Abstract Purpose: To compare the clinical characteristics and overall survival (OS) of germline mutation carriers in homologous recombination repair (HRR) genes and noncarriers with pancreatic ductal adenocarcinoma (PDAC). Experimental Design: Germline DNA from 3,078 patients with PDAC enrolled in a prospective registry at Mayo Clinic between 2000 and 2017 was analyzed for mutations in 37 cancer predisposition genes. Characteristics and OS of patients with mutations in eight genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, PALB2, RAD51C, and RAD51D) involved in HRR were compared with patients testing negative for mutations in all 37 genes. Results: The 175 HRR mutation carriers and 2,730 noncarriers in the study had a median duration of follow-up of 9.9 years. HRR mutation carriers were younger (median age at diagnosis: 63 vs. 66 years, P &amp;lt; 0.001) and more likely to have metastatic disease at diagnosis (46% vs. 36%, P = 0.004). In a multivariable model adjusting for sex, age at diagnosis, and tumor staging, patients with germline HRR mutations had a significantly longer OS compared with noncarriers [HR, 0.83; 95% confidence interval (CI), 0.70–0.97; P = 0.02]. Further gene-level analysis demonstrated that germline ATM mutation carriers had longer OS compared with patients without germline mutations in any of the 37 genes (HR, 0.72; 95% CI, 0.55–0.94; P = 0.01). Conclusions: This study demonstrates that germline mutation carrier status in PDAC is associated with longer OS compared with noncarriers. Further research into tumor biology and response to platinum-based chemotherapy in germline mutation carriers with PDAC are needed to better understand the association with longer OS.
Roles of the complement system in alcohol-induced liver disease
Authors: Yi Zhou, Guandou Yuan, Fudi Zhong, Songqing He
Journal: Clinical and Molecular Hepatology (2020)

Alcohol-induced liver disease (ALD) is a complex disorder, with a disease spectrum ranging from steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Although the pathogenesis of ALD is incompletely understood and currently no effective drugs are available for ALD, several lines of evidence suggest that complement activation and oxidative stress play crucial roles in the pathogenesis of ALD. Complement activation can regulate the production of ROS and influence oxidative stress in ALD. Precise regulation of the complement system in ALD may be a rational and novel avenue to postpone and even reverse the progression of disease and simultaneously promote the repair of liver injury. In this mini-review, we briefly summarize the recent research progress, especially focusing on the role of complement and oxidative stress-induced transfer RNA-derived fragments, which might help us to better understand the pathogenesis of ALD and provide aid in the development of novel therapeutic strategies for ALD.
Time for More Inclusive Cancer Trials
Authors: Piet Dirix, Lynda Wyld, Shani Paluch-Shimon, Philip Poortmans
Journal: Journal of the National Comprehensive Cancer Network (2020)

I n this issue of JNCCN, Abi Jaoude et al 1 convincingly demonstrate that re- cruitment in randomized oncologic clinical trials is typically limited to patients with good performance status (PS).Indeed, in their review of 600 trials, the vast majority (96.3%) of included patients had excellent PS (ECOG PS score 0 or 1).Certainly this is not consistent with daily clinical reality and, together with previously well-described age, sex, and race biases that are inherent in clinical trials, could severely limit the generalizability of trial results to routine clinical practice. 2Their thought-provoking analysis should encourage not only researchers and clinicians but also regulatory bodies, funders, and patient advocates to reflect critically about potentially serious biases in the processes to evaluate, approve, and reimburse new cancer treatments.
Implementing teleoncology in a safety-net hospital during the COVID-19 pandemic.
Authors: Andrew James Wiele, Tejal Amar Patel, Kristyn-Mae Russo, Sarah Rizvi, Patricia De Los Rios, Robert Harrison Hester, Demetria Joy Smith-Graziani, Hilary Y. Ma, Alyssa G. Rieber
Journal: Journal of Clinical Oncology (2020)

262 Background: In response to the COVID-19 pandemic, telehealth has emerged as a key strategy to ensure the safety of patients and healthcare workers and minimize disease spread. Lyndon B. Johnson Hospital (LBJ) is a safety-net hospital that mainly serves low income and uninsured patients (pts), and MD Anderson Medical Oncology faculty and fellows diagnose and treat over 800 new cancer cases per year in the LBJ Oncology Clinic. We piloted a teleoncology (TO) program to replace in-person visits for pts with clinic appointments (appts) during the COVID-19 pandemic. Methods: A multidisciplinary team was formed to implement TO in the LBJ Oncology Clinic. Fellows and APPs screened their appts in advance and used guidelines to determine pts appropriate for TO. Clinic visits were prioritized for new pts, treatment consents, and symptomatic pts; stable pts on treatment and surveillance had appts changed to TO. Pts were notified when their appts were converted, with integrated video visits preferred over telephone visits. To limit disease exposure, 3 fellows rotated in clinic for one week at a time and cared for the pooled clinic pts; the other 16 fellows and 2 APPs conducted TO and remotely staffed their pts with faculty on their assigned clinic day. We reviewed TO visits during the initial 1-month pilot period and survey results from involved personnel. Results: From 4/13/2020 – 5/8/2020, we identified 251 pts that utilized TO. Median age was 57 years (range, 20-88) and 66% were female; 63% were Hispanic and 21% were African American; 52% spoke Spanish and 46% spoke English. 57% of TO visits were conducted via telephone and 43% via video. 48% of the TO visits were for pts on active treatment, including IV therapy (35%) and oral targeted agents (13%); 15% were surveillance pts with (9%) or without (6%) restaging imaging, 8% were pts on endocrine therapy, and 16% had transitioned to the Survivorship Clinic staffed with APPs. Survey response rate was 100% (5/5) for faculty, 74% (14/19) for fellows, and 100% (2/2) for APPs. 80% of faculty, 57% of fellows, and 100% of APPs were generally satisfied (agree/strongly agree) with the patient care delivered via TO; 100% of faculty, 64% of fellows, and 100% of APPs believe patients were generally satisfied with TO. Conclusions: This study demonstrates that implementing TO in a fellows’ teaching clinic at a safety-net hospital is feasible and effective. Nearly half of the TO visits conducted during this pilot period were for pts on active cancer treatment and the majority of caregivers were satisfied with TO. Pt care via TO is ongoing and pt survey data is currently being collected.
Targeting hepatocyte growth factor/c‐mesenchymal–epithelial transition factor axis in hepatocellular carcinoma: Rationale and therapeutic strategies
Authors: Jianqing Yu, George G. Chen, Paul B. S. Lai
Journal: Medicinal Research Reviews (2020)

Abstract Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide. The outcome of current standard treatments, as well as targeted therapies in advanced stages, are still unsatisfactory. Attention has been drawn to novel strategies for better treatment efficacy. Hepatocyte growth factor/c‐mesenchymal–epithelial transition factor (HGF/c‐Met) axis has been known as an essential element in the regulation of liver diseases and as an oncogenic factor in HCC. In this review, we collected the evidence of HGF/c‐Met as a tumor progression and prognostic marker, discussed the anti‐c‐Met therapy in vitro, summarized the outcome of c‐Met inhibitors in clinical trials, and identified potential impetus for future anti‐c‐Met treatments. We also analyzed the inconsistency of HGF/c‐Met from various publications and offered reasonable explanations based on the current understanding in this area. In conclusion, HGF/c‐Met plays a crucial role in the progression and growth of HCC, and the strategies to inhibit this pathway may facilitate the development of new and effective treatments for HCC patients.