tbuckley/cabot-search huggingface dataset:
Feasibility, delivery, and acceptance of a multidisciplinary survivorship care model based in an Asian national ambulatory cancer center: A six-month review.
Authors: Yu Ke, Patricia Soek Hui Neo, Kiley Loh, Grace Meijuan Yang, Shirlynn Ho, Yee Pin Tan, Mothi Babu Ramalingam, Daniel Quah, Lita Chew, Phebe Si, Yung Ying Tan, Beng Choo Tay, Suzanne Poh Geok Koh, Alexandre Chan
Journal: Journal of Clinical Oncology (2020)

34 Background: Accessible Cancer Care to Enable Support for Cancer Survivors (ACCESS) is a multidisciplinary survivorship care model launched at the National Cancer Centre Singapore, the largest ambulatory cancer centre serving 70% of adult cancer patients in the public sector. ACCESS employs routine distress screening to triage patients with varying care needs and complexities. This study aims to examine the feasibility, delivery, and acceptance of ACCESS in providing appropriate service referrals to cancer patients in clinical settings. Methods: As part of an ongoing evaluation, we evaluated ACCESS for a 6-month implementation period between September 2019 and February 2020. Feasibility was assessed by proportions of (1) eligible breast and gynecological cancer patients who completed the locally adapted Distress Thermometer (DT) screening tool, (2) highly distressed patients, and (3) highly distressed patients requiring multidisciplinary meetings (MDM). Delivery was characterized by the mode and number of supportive care team (SCT) reviews required. Acceptance rates of SCT reviews by distressed patients and the uptake rate of service referrals recommended by the SCT were tabulated. Results: ACCESS screened 1074/1471 (73.0%) of all eligible patients within the 6-month period and identified 239/1074 (22.3%) as highly distressed for follow-up with the SCT. Eventually, 84.5% agreed to SCT review, with approximately one-fourth (26.7%) requiring MDM reviews. The majority (62.4%) of all distressed patients were identified at their first DT completion, whereas 19.8% and 7.4% were identified at their second and third completions respectively. The most common modes of follow-up were phone reviews (49.9%) and face-to-face in clinic waiting areas (48.6%). The SCT recommended 80 referrals to distressed patients for the following services: psychosocial (27.2%), cancer rehabilitation (5.9%), and home hospice (5.0%). The acceptance rates of the referrals for psychosocial, rehabilitation, and hospice services were 43.6%, 75.0%, and 80.0% respectively. Conclusions: ACCESS is a feasible model for triaging Asian cancer patients based on distress levels, and identifying complex patients requiring care personalization through MDM. The poorer acceptance rate of psychosocial services highlights patients’ preference for interventions targeting physical than psychosocial issues. Future studies should explore whether the uptake of psychosocial services is higher in the post-COVID era.
Breast cancer-induced immune suppression in the sentinel lymph node is effectively countered by CpG-B in conjunction with inhibition of the JAK2/STAT3 pathway
Authors: Kim M van Pul, Ronald J C L M Vuylsteke, Monique T A de Beijer, Rieneke van de Ven, M Petrousjka van den Tol, Hein B A C Stockmann, Tanja D de Gruijl
Journal: Journal for ImmunoTherapy of Cancer (2020)

We previously showed selectively hampered activation of lymph node-resident (LNR) dendritic cell (DC) subsets in the breast cancer (BrC) sentinel lymph node (SLN) to precede a state of profound T cell anergy. Reactivating these DC subsets by intratumoral delivery of the Toll-like receptor-9 (TLR9) agonist CpG-B could potentially offer a promising immune therapeutic strategy to combat this immune suppression and prevent disease spread. Unfortunately, CpG-B can limit its own immune stimulatory activity through direct TLR9-mediated activation of signal transducer and activator of transcription 3 (STAT3), pinpointed as a key regulator of immune suppression in the tumor microenvironment. Here, we have investigated whether in vitro exposure to CpG-B, with or without simultaneous inhibition of STAT3 signaling, could overcome immune suppression in BrC SLN.Immune modulatory effects of CpG-B (CPG7909) with or without the JAK2/STAT3 inhibitor (STAT3i) AG490 were assessed in ex vivo cultured BrC SLN-derived single-cell suspensions (N=29). Multiparameter flow cytometric analyses were conducted for DC and T cell subset characterization and assessment of (intracellular) cytokine profiles. T cell reactivity against the BrC-associated antigen Mammaglobin-A was determined by means of interferon-γ ELISPOT assay.Although CpG-B alone induced activation of all DC subsets, combined inhibition of the JAK2/STAT3 pathway resulted in superior DC maturation (ie, increased CD83 expression), with most profound activation and maturation of LNR DC subsets. Furthermore, combined CpG-B and JAK2/STAT3 inhibition promoted Th1 skewing by counterbalancing the CpG-induced Th2/regulatory T cell response and significantly enhanced Mammaglobin-A specific T cell reactivity.Ex vivo immune modulation of the SLN by CpG-B and simultaneous JAK2/STAT3 inhibition can effectively overcome BrC-induced immune suppression by preferential activation of LNR DC, ultimately restoring type 1-mediated antitumor immunity, thereby securing a BrC-specific T cell response. These findings provide a clear rationale for clinical exploration of SLN-immune potentiation through local CpG/STAT3i administration in patients with BrC.
Abstract 12518: Bicuspid Aortic Valve Disease Increases Viscous Energy Loss, Circumferential Wall Shear Stress, and Pressure Drop in the Ascending Aorta
Authors: Patrick Geeraert, Jacqueline Flewitt, Michael Bristow, Bobak Heydari, Carmen Lydell, Andrew G Howarth, Ali Fatehi, Paul Fedak, James White, Julio Garcia
Journal: Circulation (2019)

Introduction: We use 4D-Flow MRI to investigate the effects of bicuspid aortic valve (BAV) disease on downstream pressure drop (PD), wall shear stress (WSS), and viscous energy loss (EL) in the asc...
Ovarian cancer patients’ perspectives on facilitators and barriers to accessing financial assistance.
Authors: Margaret Irene Liang, Janice Leahgrace Simons, Ivan I. Herbey, Jaclyn Wall, Lindsay Rucker, Nataliya V. Ivankova, Maria Pisu, Warner King Huh
Journal: Journal of Clinical Oncology (2020)

64 Background: Our aim was to obtain ovarian cancer patients’ perspective on accessing financial assistance programs. Methods: We recruited ovarian cancer patients receiving systemic therapy who screened positive for financial distress using Comprehensive Score for Financial Toxicity &lt;26. Two interviewers conducted 45-minute interviews on the costs of care, which were recorded and transcribed. Three coders used inductive thematic analysis to identify themes. Results: There were 18 of 22 interviews currently evaluable. Median age was 57 and 68% of participants reported income &lt;$40,000. Facilitators and barriers to accessing financial assistance are shown in the table below. Conclusions: Patients’ reliance on existing support systems and cancer organizations highlight a need for health systems to leverage these relationships and improve organized efforts to provide information related to financial assistance. Proactively asking about financial needs and providing resources to all patients, regardless of income, may mitigate patient reported barriers to accessing financial assistance. [Table: see text]
Analysis of Genomic Characteristics and Transmission Routes of Patients With Confirmed SARS-CoV-2 in Southern California During the Early Stage of the US COVID-19 Pandemic
Authors: Wenjuan Zhang, John Paul Govindavari, Brian D. Davis, Stephanie S. Chen, Jong Taek Kim, Jianbo Song, Jean Lopategui, Jasmine T. Plummer, Eric Vail
Journal: JAMA Network Open (2020)

In late December 2019, an outbreak of a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China. Data on the routes of transmission to Los Angeles, California, the US West Coast epicenter for coronavirus disease 2019 (COVID-19), and subsequent community spread are limited.To determine the transmission routes of SARS-CoV-2 to Southern California and elucidate local community spread within the Los Angeles metropolitan area.This case series included 192 consecutive patients with reverse transcription-polymerase chain reaction (RT-PCR) test results positive for SARS-CoV-2 who were evaluated at Cedars-Sinai Medical Center in Los Angeles, California, from March 22 to April 15, 2020. Data analysis was performed from April to May 2020.SARS-CoV-2 viral genomes were sequenced. Los Angeles isolates were compared with genomes from global subsampling and from New York, New York; Washington state; and China to determine potential sources of viral dissemination. Demographic data and outcomes were collected.The cohort included 192 patients (median [interquartile range] age, 59.5 [43-75] years; 110 [57.3%] men). The genetic characterization of SARS-CoV-2 isolates in the Los Angeles population pinpointed community transmission of 13 patients within a 3.81 km2 radius. Variation landscapes of this case series also revealed a cluster of 10 patients that contained 5 residents at a skilled nursing facility, 1 resident of a nearby skilled nursing facility, 3 health care workers, and a family member of a resident of one of the skilled nursing facilities. Person-to-person transmission was detected in a cluster of 5 patients who shared the same single-nucleotide variation in their SARS-CoV-2 genomes. High viral genomic diversity was identified: 20 Los Angeles isolates (15.0%) resembled SARS-CoV-2 genomes from Asia, while 109 Los Angeles isolates (82.0%) were similar to isolates originating from Europe. Analysis of other common respiratory viral pathogens did not reveal coinfection in the cohort.These findings highlight the precision of detecting person-to-person transmission and accurate contact tracing directly through SARS-CoV-2 genome isolation and sequencing. Development and application of phylogenetic analyses from the Los Angeles population established connections between COVID-19 clusters locally and throughout the US.
Using machine learning to identify older adults at high risk for hospitalization and mortality via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
Authors: Huiwen Xu, Supriya Gupta Mohile, Marie Anne Flannery, Luke Joseph Peppone, Mostafa Mohamed, Erika E. Ramsdale, Amita Patil, Sahithi Jonnalagadda, Leah Jamieson, Victor G. Vogel, Khalil Katato, Bianca Hall, Karen Michelle Mustian, Eva Culakova
Journal: Journal of Clinical Oncology (2020)

169 Background: PRO-CTCAE captures symptomatic adverse events (e.g. pain, fatigue) and may indicate poor treatment tolerability in older patients (pts) with advanced cancer. Using unsupervised machine learning which can detect unknown patterns in data, we aimed to evaluate if clusters identified based on PRO-CTCAE severity were associated with hospitalization and survival. Methods: We included pts randomized to the control arm of GAP 70+ (URCC 13059; PI: Mohile), which enrolled pts aged ≥70, with incurable solid tumors or lymphoma, and ≥1 geriatric assessment (GA) domain impairment starting a new treatment regimen. Measures included 24 PRO-CTCAE items (v1.0) with severity attributes (item 0-4; total score 0-96, higher score = greater severity). The unsupervised algorithm (K-means with Euclidean Distance) clustered pts at baseline based on similarities of severities of the 24 items. We examined if the clusters were associated with treatment-related hospitalization within 3 months and lower survival at 6 months using Logistic and Cox regressions. Results: Of the 369 control pts, 366 completed GA and PRO-CTCAE at baseline (mean age 77.2, 94.3% white, 30.9% with GI and 31.4% with lung cancer; mean number of impaired GA 4.4). By PRO-CTCAE, the most prevalent symptoms were fatigue (82.7%), pain (60.9%), and decreased appetite (58.7%). Greater GA impairment was associated with 20 PRO-CTCAE items (fatigue, pain, and decreased appetite having the strongest associations; all Pearson's r &gt; 0.33). Three clusters were identified: Low Severity (51.4%); Moderate Severity (34.4%), and High Severity (14.2%). Mean total severity score was 6.9 (low), 16.9 (moderate), and 28.7 (high), respectively (p &lt; 0.01). No difference in demographics was found among clusters. Percent of pts hospitalized were 21.3% (low), 36.5% (moderate), and 38.5% (high) (p &lt; 0.01); survival rates were 81.9% (low), 71.4% (moderate), and 55.3% (high) (p &lt; 0.01). Controlling for cancer type and GA, compared to pts in Low Severity cluster, pts in Moderate and High Severity were more likely to be hospitalized (odds ratio = 1.77, p = 0.03); pts in High Severity cluster were more likely to die (hazard ratio = 2.23, p = 0.01). Conclusions: Unsupervised machine learning was able to partition pts into different PRO-CTCAE severity clusters; pts with higher baseline severity were more likely to be hospitalized or die. PRO-CTCAE provides additional information to GA. Funding: R01CA177592, U01CA233167, UG1CA189961.
Novel Methylated DNA Markers in the Surveillance of Colorectal Cancer Recurrence
Authors: Hao Xie, Douglas W. Mahoney, Patrick H. Foote, Kelli N. Burger, Karen A. Doering, William R. Taylor, Sara S. Then, Xiaoming Cao, Maria McGlinch, Calise K. Berger, Tsung-Teh Wu, Joleen M. Hubbard, Hatim T. Allawi, Michael W. Kaiser, Graham P. Lidgard, David A. Ahlquist, John B. Kisiel
Journal: Clinical Cancer Research (2020)

Abstract Purpose: We aimed to assess the concordance of colorectal cancer–associated methylated DNA markers (MDM) in primary and metastatic colorectal cancer for feasibility in detection of distantly recurrent/metastatic colorectal cancer in plasma. Experimental Design: A panel of previously discovered colorectal cancer–associated MDMs was selected. MDMs from primary and paired metastatic colorectal cancer tissue were assayed with quantitative methylation-specific PCR. Plasma MDMs were measured blindly by target enrichment long-probe quantitative-amplified signal assays. Random forest modeling was used to derive a prediction algorithm of MDMs in archival plasma samples from primary colorectal cancer cases. This algorithm was validated in prospectively collected plasma samples from recurrent colorectal cancer cases. The accuracy of the algorithm was summarized as sensitivity, specificity, and area under the curve (AUC). Results: Of the 14 selected MDMs, the concordance between primary and metastatic tissue was considered moderate or higher for 12 MDMs (86%). At a preset specificity of 95% (91%–98%), a panel of 13 MDMs, in plasma from 97 colorectal cancer cases and 200 controls, detected stage IV colorectal cancer with 100% (80%–100%) sensitivity and all stages of colorectal cancer with an AUC of 0.91 (0.87–0.95), significantly higher than carcinoembryonic antigen [AUC, 0.72 (0.65–0.79)]. This panel, in plasma from 40 cases and 60 healthy controls, detected recurrent/metastatic colorectal cancer with 90% (76%–97%) sensitivity, 90% (79%–96%) specificity, and an AUC of 0.96 (0.92–1.00). The panel was positive in 0.30 (0.19–0.43) of 60 patients with no evidence of disease in post-operative patients with colorectal cancer. Conclusions: Plasma assay of novel colorectal cancer–associated MDMs can reliably detect both primary colorectal cancer and distantly recurrent colorectal cancer with promising accuracy.
Impact of a hospital conversion to COVID-19 center on cancer care of patients in a urologic oncology clinic in Mexico
Authors: Salvador G. Santiesteban, Haydee Verduzco-Aguirre, Christianne Bourlon, Maria T. Bourlon
Journal: Clinical Cancer Research (2020)

Background: COVID-19 has been a challenge for health systems worldwide  Many hospitals were converted intoCOVID-19 centers, including our center  Diagnostic studies, ambulatory procedures, and elective surgeries werecanceled, and emergency care and inpatient services were closed for patients without COVID-19  Lack of access tohospital services represents a problem in the care of cancer, especially in low- and middle-income countries(LMICs)  Our aim was to analyze the impact of hospital conversion to a COVID-19 center on the follow-up andmanagement of patients in our urologic oncology clinic  Methods: We analyzed data of all patients in our urologic oncology clinic with appointments scheduled from March16th to May 31st  A fellow reviewed all cases to evaluate if appointments were eligible for regular visit, telemedicine, or postponement and patients were contacted  Demographic, disease, and treatment characteristics were obtained Population was analyzed according to type of visit (standard of care vs  clinical trial)  We examined univariateassociations between groups  A p-value ≤0 05 indicated statistical significance  Results: A total of 336 patients were included;the median age was 65 (18-94) years, and 306 (91 1%) were men The main neoplasms were prostate (49 4%), kidney (20 2%), germ cell tumors (21 4%), urothelial (8 6%), and penile(0 3%) cancer  46 7% of patients were in active treatment, and 11 9% were enrolled in a clinical trial  Remotecommunication was established with 184/224 (82 1%) patients  We planned to reschedule the visits of 224/336(66 7%) patients  Medical appointments were rescheduled to a median of 91 days (IQR 65-105 days)  All patientsenrolled in clinical trials visited the clinic as scheduled  Among patients eligible for telemedicine, 105 (46 9%) wereon surveillance, 68 (30 4%) on hormone therapy, 45 (20 1%) on no active treatment, and 6 (2 7%) on other therapy The majority of the 111 patients who had an in-person appointment were receiving chemotherapy (24 3%), followedby immunotherapy (15 3%), targeted therapy (15 3%), and hormone therapy (13 5%)  13 5% had no activetreatment and 9 0% were on surveillance  Comparing non-protocol versus protocol patients, we found a significantdifference in loss of follow-up (12 2% vs 0% p = 0 012)  During the study period, two (0 6%) confirmed cases andone (0 3%) death due to COVID-19 were recorded  Conclusions: In our initial experience, rescheduling of visits and remote follow-up was possible in most patientsduring hospital conversion to a COVID-19 center  Despite the constrained resources and communication barriers ofLMICs, the rate of patients lost to follow-up was not increased during the pandemic in our center  Telemedicine waspossible, particularly for those on surveillance and hormone therapy  Comparing standard clinical care versusclinical trial patients, we found a significant difference in terms of loss to follow-up
Proton beam radiotherapy vs. radiofrequency ablation for recurrent hepatocellular carcinoma: A randomized phase III trial
Authors: Tae Hyun Kim, Young Hwan Koh, Bo Hyun Kim, Min Ju Kim, Ju Hee Lee, Boram Park, Joong-Won Park
Journal: Journal of Hepatology (2020)

Proton beam radiotherapy (PBT) has recently been applied to treat hepatocellular carcinoma (HCC); however, there is no randomized controlled trial-based evidence on its safety and efficacy. We compared the outcomes of PBT and radiofrequency ablation (RFA) in patients with recurrent/residual HCC (rHCC) in a phase III non-inferiority trial.Patients with rHCC (size <3 cm, number ≤2) were randomly assigned to receive PBT or RFA according to Child-Pugh score and tumor stage. After randomization, if the assigned treatment was technically infeasible, crossover was allowed. The primary endpoint was 2-year local progression-free survival (LPFS), with a non-inferiority margin of 15% in the per-protocol (PP) population; a complementary analysis was performed in the intention-to-treat (ITT) population (NCT01963429).The ITT population comprised 144 patients receiving either PBT (n = 72) or RFA (n = 72). Six patients switched from the PBT arm to the RFA arm and 19 patients switched from the RFA arm to the PBT arm. In the PP population, the 2-year LPFS rate with PBT (n = 80) vs. RFA (n = 56) was 94.8% vs. 83.9%, a difference of 10.9 percentage points (90% CI 1.8-20.0; p <0.001); in the ITT population, the 2-year LPFS rate with PBT vs. RFA was 92.8% vs. 83.2%, a difference of 9.6 percentage points (90% CI 0.7-18.4; p <0.001), meeting the criteria for non-inferiority. The 3- and 4-year LPFS rates for PBT were also non-inferior to those for RFA. The most common adverse events were radiation pneumonitis (32.5%) and decreased leukocyte counts (23.8%) for PBT and increased alanine aminotransferase levels (96.4%) and abdominal pain (30.4%) for RFA. No Grade 4 adverse events or mortality were noted.PBT showed LPFS values that were non-inferior to those for RFA; in addition, PBT was tolerable and safe. CLINICAL TRIAL NUMBER: #NCT01963429 (ClinicalTrials.gov).Radiofrequency ablation is the standard of care for patients with small hepatocellular carcinoma in whom surgery is not feasible. This study is the first phase III randomized controlled trial to evaluate the clinical outcomes of proton beam radiotherapy vs. radiofrequency ablation in patients with recurrent small HCC. Our findings show that this new technique is not inferior and can be applied safely in patients with small recurrent hepatocellular carcinoma.
Personalising exercise recommendations for healthy cognition and mobility in aging: time to address sex and gender (Part 1)
Authors: Cindy K Barha, Ryan S Falck, Søren T Skou, Teresa Liu-Ambrose
Journal: British Journal of Sports Medicine (2020)

Impaired cognition and mobility are common in older adults and they often coexist due to shared pathophysiology.1 Worldwide, one new case of dementia is detected every 3 s.2 Exercise improves cognitive function and reduces the risk of mobility disability and falls.3–5

Leaders in physical activity and exercise research are aiming to delineate what (e.g., type, duration, frequency and intensity) exercise should be recommended and when (e.g., midlife versus late life) it is best done for promoting cognitive and mobility outcomes in healthy individuals and in those at risk for cognitive impairment. Two other key questions are how (e.g., neurotrophic factors, cardiovascular fitness) and for whom (e.g., biological sex, gender) does exercise benefit cognition and mobility. Understanding mediators (i.e., how) could help maximise gains by enhancing intervention elements that impact key mechanisms at lower cost and/or risk. Identifying moderators (e.g., who, when)—factors that either attenuate or amplify the effects of exercise—will enable precise recommendations for individuals with similar characteristics (i.e., subgroups).

In this two-part editorial series, we focus on for whom factors that may moderate the effect of exercise on cognitive function and mobility outcomes. In Part 1, we focus on biological sex and gender. Biological sex is defined as the genetics, gonadal hormones and phenotype resulting from XX versus XY chromosomes. Gender refers to the social, environmental, cultural and behavioural factors that influence individual actions and experiences. In Part 2, …