tbuckley/cabot-search huggingface dataset:
Patient and treatment characteristics of emergency presentations due to immune-mediated toxicities.
Authors: Sharon Hyo-Eun Nahm, Richard Heywood, Sophia Callaghan, Patricio Serra-Bellver, Avinash Gupta, Tim Cooksley, Paul Lorigan
Journal: Journal of Clinical Oncology (2021)

6586 Background: The prevalence of immune-mediated toxicities from immune checkpoint inhibitors (ICIs) is well described. However, the characteristics and treatment patterns for patients with emergency presentations due to immune-mediated toxicity are less well known. Methods: This study of all emergency presentations in patients treated with ICIs was performed at The Christie NHS Foundation Trust, Manchester, United Kingdom from May 2018-February 2020. The aims were to describe the patient and treatment characteristics of those diagnosed with an immune-mediated toxicity. Results: In total, 597 patients receiving ICIs had an emergency presentation and 191/597 (32%) were diagnosed with an immune-mediated toxicity. Of these patients, the median age was 64 years and 127/191 (67%) were male. The most common tumour types were melanoma (53%) and lung (22%) and the most common ICI received was ipilimumab + nivolumab combination immunotherapy (42%), followed by pembrolizumab monotherapy (21%) and nivolumab monotherapy (20%). The median number of cycles received was 3 (range 1-54), and 73/191 (38%) previously had ≥ grade 2 immune-mediated toxicity. The most common diagnoses were colitis (38%), hepatitis (15%), and pneumonitis (14%). The majority, 180/191 (94%) received steroids and 52/180 (29%) patients required second-line immunosuppression. The most common second-line immunosuppressants used were mycophenolate mofetil (58%) and infliximab (50%). Eleven patients (22%) required more than one second-line immunosuppressant. Conclusions: The majority of patients with emergency presentations due to immune-mediated toxicity were being treated with combination immunotherapy for melanoma. More than a third of patients had previous ≥ grade 2 immune-mediated toxicity. Over one quarter of patients treated with steroids required second-line immunosuppression. Identifying these characteristics can help inform which patients receiving ICIs seeking medical review need admission to a center with experience in managing immune-mediated toxicity.
Sinomenine ester derivative inhibits glioblastoma by inducing mitochondria-dependent apoptosis and autophagy by PI3K/AKT/mTOR and AMPK/mTOR pathway
Authors: Xiangjin Zheng, Wan Li, Huanli Xu, Jinyi Liu, Liwen Ren, Yihui Yang, Sha Li, Jinhua Wang, Tengfei Ji, Guanhua Du
Journal: Acta Pharmaceutica Sinica B (2021)

Glioblastoma multiforme (GBM) in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it. Studies of sinomenine, an alkaloid from the Chinese medicinal plant, Sinomenium acutum, showed that it had inhibitory effects on several kinds of cancer. Here, we synthesized a sinomenine derivative, sino-wcj-33 (SW33), tested it for antitumor activity on GBM and explored the underlying mechanism. SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells. It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis. Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body. SW33 also induced autophagy through the PI3K/AKT/mTOR and AMPK/mTOR pathways. Thus, SW33 appears to be a promising drug for treating GBM effectively and safely.
Health-related unemployment trends among survivors of childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: Neel S. Bhatt, Pamela Goodman, Wendy M. Leisenring, Gregory T. Armstrong, Eric Jessen Chow, Melissa M. Hudson, Kevin R. Krull, Paul C. Nathan, Kevin C. Oeffinger, Leslie L. Robison, Anne C. Kirchhoff, Daniel A. Mulrooney
Journal: Journal of Clinical Oncology (2021)

10048 Background: The impact of treatment era and chronic health conditions on health-related unemployment among childhood cancer survivors has not been studied. Methods: Childhood cancer survivors (age ≥25 years) enrolled in the CCSS (3,420 diagnosed in the 1970s, 3,564 in the 1980s, and 2,853 in the 1990s) were matched 1:5 on sex, race/ethnicity, census bureau division, age, and year of survey to the Behavioral Risk Factor Surveillance System (BRFSS), a nationally representative population. Among survivors, health-related unemployment was defined as self-reported unemployment due to illness/disability and for BRFSS participants as self-reported inability to work. To standardize follow-up, health-related unemployment was assessed either in 2002-05 or 2014-16 for both cohorts. Sex stratified standardized prevalence ratio (SPR) and relative SPR (rSPR) with 95% confidence intervals (CI) for health-related unemployment were estimated using multivariable generalized linear models, with BRFSS background rates to assess the impact of treatment era and moderate to severe health conditions (per the Common Terminology Criteria for Adverse Events). Results: Prevalence of health-related unemployment in survivors (median age 9 years [range 0-20] at diagnosis and 33 years [25-54] at follow-up) was significantly higher compared to BRFSS participants (females: 11.3% vs 3.7%; SPR 3.0, 95% CI 2.7-3.3; males: 10.5% vs 3.0%; SPR 3.5, 95% CI 3.1-3.9). Health-related unemployment risks declined among survivors in more recent decades (p trend &lt; 0.001) for females: 1970s SPR 3.8, 95% CI 3.2-4.5, 1980s SPR 2.9, 95% CI 2.5-3.5, 1990s SPR 2.5, 95% CI 2.1-3.0; and males: 1970s SPR 3.6, 95% CI 2.9-4.4, 1980s SPR 3.8, 95% CI 3.1-4.7, 1990s SPR 3.0, 95% CI 2.5-3.7. Among survivors, multivariable models identified associations between presence of specific health conditions and elevated health-related unemployment (Table) adjusting for all statistically significant health conditions, race/ethnicity, treatment era, age at survey, and diagnosis. Among females, rSPR for endocrine conditions differed between 1970s and 1990s (interaction p = 0.04); fewer significant health conditions remained in the final model for males. Conclusions: While prevalence for health-related unemployment has declined over time, childhood cancer survivors remain at higher risk compared to the general population. These elevated risks are associated with chronic health conditions and affect female survivors more than male survivors.[Table: see text]
Novel concept of exosome-like liposomes for the treatment of Alzheimer's disease
Authors: Mário Fernandes, Ivo Lopes, Luana Magalhães, Marisa P. Sárria, Raul Machado, João Carlos Sousa, Cláudia Botelho, José Teixeira, Andreia C. Gomes
Journal: Journal of Controlled Release (2021)
Code status and outcomes in patients with cancer and COVID-19: A COVID-19 and cancer consortium (CCC19) registry analysis.
Authors: Elizabeth Trice Loggers, Elizabeth Marie Wulff-Burchfield, Ishwaria Mohan Subbiah, Ali Raza Khaki, Pamela Egan, Dimitrios Farmakiotis, Hardeep Phull, Elizabeth Nakasone, Chris Labaki, Peter Paul Yu, Monika Joshi, Elizabeth A. Griffiths, Trisha Michel Wise-Draper, Chinmay Jani, Astha Thakkar, Matthew Puc, Clara Hwang, Blanche H. Mavromatis, Dimpy P Shah, Jeremy Lyle Warner
Journal: Journal of Clinical Oncology (2021)

12035 Background: In-hospital mortality among patients with cancer (pts) and COVID-19 infection is high. The frequency of, and factors associated with, do-not-resuscitate (DNR) or do-not-intubate (DNI) orders at hospital admission (HA), and their correlation with care, has not been well studied. In November 2020, we began collecting this information for pts who were hospitalized at initial presentation in the CCC19 registry (NCT04354701). Methods: We investigated: 1. the frequency of, and factors associated with, DNR/DNI orders at HA; 2. change in code status during HA; and 3. the correlation between DNR/DNI orders and palliative care consultation (PC), mortality or length of stay (LOS). We included hospitalized, adult pts with cancer and COVID-19 from 57 participating sites. Reported characteristics include age, ECOG performance status (PS), and cancer status. Comparative statistics include 2-sided Wilcoxon rank sum and Fisher’s exact tests. Results: 744 pts had known baseline and/or changed code status (CS); most (79%) maintained their baseline CS (Table). Those with DNR±DNI orders at HA were older (median age 79 vs 69 yrs, p&lt;0.001) and more likely to have: ECOG PS 2+ vs 0-1 (45% vs 22%, OR 3.95, p&lt;0.001), metastatic disease (45% vs 35%, OR 1.72, p=0.005) and progressing cancer (32% vs 16%, OR 2.69, p&lt;0.001), but equally likely to have received systemic anticancer therapy in the prior 3 months (38% vs 45%, p=0.15). N=192 pts with a change in CS from full to DNR±DNI were younger (median age 73), had better PS (37% ECOG PS 2+), and were less likely to have progressing cancer (23%) than those with DNR±DNI orders at baseline. However, their LOS was significantly longer, median 9 vs 6 days, p&lt;0.001. Compared to those with DNR±DNI orders at HA, pts whose CS changed to DNR±DNI were more likely to die, OR 2.94, 95% CI 1.76-4.97, p&lt;0.001. PC was obtained in 106 (14%) pts and associated with transition to DNR±DNI in 47 (44%), affirmation of admission CS in 58 (55%), and reversal in 1 (1%). Median LOS for pts receiving PC was 11 vs 6 days, p&lt;0.001. Conclusions: In our sample, the majority of patients with cancer and COVID-19 were full code at hospital admission. DNR±DNI status, whether at baseline or assigned during the hospital course, was associated with worse prognosis. Longer length of stay for patients changing code status and/or receiving palliative care consultation was observed likely suggesting earlier palliative care consultation is an important, but likely underutilized component in the care of patients with cancer and COVID-19.[Table: see text]
Various treatment options for the management of Campanacci III giant cell bone tumor.
Authors: Syed Faraz-ul-Hassan Shah Gillani, Muhammad Taqi, Muhammad Ayyaz Ul Haq, Anam Aslam, Faisal Masood, Mobeen Zaka Haider, Muhammad Umair Mushtaq
Journal: Journal of Clinical Oncology (2021)

e23509 Background: To assess the treatment effectiveness of Campanacci III giant cell bone tumours. Methods: This prospective cohort study was done using a non-probability purposive sampling technique in the orthopaedic surgery and traumatology unit-I department from February 2013 to October 2017. The sample size of 21 patients aged 33 to 60year Campanacci III giant cell bone tumour diagnosed on biopsy were included, and all patients with uncontrolled diabetes mellitus, decompensated liver disease, chronic renal failure, previously treated for giant cell tumours and malignant transformation were excluded. Treatment options included wide margin excision with fibular vascular graft with plating, mega prosthesis, and chirolin prosthesis. Treatment effectiveness was observed in terms of superficial &amp; deep infection, limb length discrepancy, implant failure and function using musculoskeletal tumour society rating scale (MSTS). Follow-p of the patients was five years. All patients were followed up for six months in the first year and yearly till five years. Results: Out of the total 21 patients, male were 11 (52.4%) and female were 10 (47.6%). The mean age of the patients was 34.8±14.6 years, with a median age was 30year. Four (19.1%) had proximal humerus, o5 (23.8% had distal radius, 09 (42.8% had distal femur, and 03 (14.3%) had proximal thigh involvement. The MSTS was 21.8±6.8 with a median score of 22 till the last follow-up. Kaplan Meier curve was plotted, and median survival rate was 50% at 54 months for the patients treated with fibular vascular graft, 57 months for mega prosthesis and 58 months for the patients treated with chirolin prosthesis. Conclusions: Treatment of Campanacci III with mega prosthesis, fibular vascular graft and chirolin prosthesis is a good outcome except with implant failure in mega prosthesis and limb length inequality with fibular vascular grafts. [Table: see text]
Erratum to: The year in basic vascular biology research: from mechanoreceptors and neutrophil extracellular traps to smartphone data and omics
Authors: Paul Evans, Johann Wojta, Imo E Hoefer, Johannes Waltenberger, Tomasz Guzik, Lina Badimon
Journal: Cardiovascular Research (2021)

2020 has been an extraordinary year. The emergence of COVID-19 has driven urgent research in pulmonary and cardiovascular science and other fields. It has also shaped the way that we work with many experimental laboratories shutting down for several months, while bioinformatics approaches and other large data projects have gained prominence. Despite these setbacks, vascular biology research is stronger than ever. On behalf of the European Society of Cardiology Council for Basic Cardiovascular Science (ESC CBCS), here we review some of the vascular biology research highlights for 2020. This review is not exhaustive and there are many outstanding vascular biology publications that we were unable to cite due to page limits. Notwithstanding this, we have provided a snapshot of vascular biology research excellence in 2020 and identify topics that are in the ascendency and likely to gain prominence in coming years.
Association between perceptions of prognosis and end-of-life outcomes for patients with advanced lung and gastrointestinal cancer.
Authors: Carlisle E. W. Topping, Madeleine Elyze, Rachel Plotke, Lauren Heuer, Charu Vyas, Joseph A. Greer, Ryan David Nipp, Jennifer S. Temel, Areej El-Jawahri
Journal: Journal of Clinical Oncology (2021)

6503 Background: Many patients with advanced cancer maintain misperceptions of their prognosis and are thus unprepared to make difficult decisions regarding their end-of-life (EOL) care. However, studies examining the associations between patients’ perceptions of their prognosis and their EOL outcomes are limited. Methods: We conducted a secondary analysis using longitudinal data from a randomized controlled trial of a palliative care intervention for patients with newly diagnosed incurable lung and non-colorectal gastrointestinal cancer. We administered the Prognosis and Treatment Perceptions Questionnaire to assess patients’ perceptions of their prognosis at baseline, week-12, and week-24, using the final assessment closest to death. We used multivariate logistic and linear regression models, adjusting for age, gender, marital status, cancer type, and randomization to the palliative care intervention, to examine the associations among patients’ perceptions of their prognosis with the following EOL care outcomes abstracted from the electronic health record: 1) hospice utilization and length-of-stay (LOS); 2) hospitalizations in the last 30 days of life; 3) receipt of chemotherapy in the last 30 days of life; and 4) location of death. Results: We enrolled 350 patients in the parent trial, of which 80.5% (281/350) died during the study period and were included in this analysis. Overall, 59.4% (164/276) of patients reported that they were terminally ill, and 66.1% (154/233) reported that their cancer was likely curable at the assessment closest to death. In multivariate analyses, patients who reported that their cancer was likely curable were less likely to utilize hospice (OR = 0.25, 95%CI 0.10-0.61, P = 0.002) or die at home (OR = 0.56, 95%CI 0.32-0.98, P = 0.043), and more likely to be hospitalized in the last 30 days of life (OR = 2.28, 95%CI 1.20-4.32, P = 0.011). In contrast, patients’ report that they were terminally ill was only associated with lower likelihood of hospitalizations in the last 30 days of life (OR = 0.52, 95%CI 0.29-0.92, P = 0.025). Patients’ perceptions of their prognosis were not associated with hospice LOS or chemotherapy administration in the last 30 days of life. Conclusions: Patients’ perceptions of their prognosis are associated with important EOL outcomes including hospice utilization, hospitalizations at the EOL, and death at home. Interventions are needed to enhance patients’ perceptions of their prognosis in order to optimize their EOL care.
Genome-wide analysis indicating cancer associated fibroblast (CAF) impacts on colorectal cancer (CRC) prognosis via immunosuppression.
Authors: Yu-feng Chen, Xiaojian Wu, Feng Gao
Journal: Journal of Clinical Oncology (2021)

3543 Background: Cancer associated fibroblast (CAF) in tumor microenvironment is associated with poor prognosis and chemo-resistance in multiple solid tumors, however, there is lack of universal measure of CAF in colorectal cancer (CRC). The aim of this study was to assess fibroblast-signature for predicting outcome and analyze relevant mechanism. Methods: A dataset including 316 CRC patients without adjuvant chemotherapy was used as the discovery cohort for the identification of prognostic fibroblast-related genes (FRGs). A total of 1,352 CRC patients were then divided into one training cohort (n = 461) and two validation cohorts (n = 338, n = 553, respectively) for the construction of fibroblast-related gene signature (FRGS) and the verification of its prognostic value in stage II/III CRC patients. Functional annotation and analysis were performed to reveal the relevant mechanism. Results: A 11-gene signature was derived, which was prognostic for stage II/III CRC patients in two validation cohort (Validation-1 cohort: HR = 1.90, 95%CI = 1.16-3.12, P&lt; 0.01; Validation-2 cohort: HR = 1.95, 95%CI = 1.39-2.73, P&lt; 0.001). High CAF risk was correlated with worse prognosis in CRC patients without adjuvant chemotherapy (HR = 3.63, 95%CI = 2.24-5.88, P&lt; 0.001), but not in patients who received adjuvant chemotherapy ( P= 0.154). Similar trends were found in Validation-1 cohort. After integrated with clinical characteristics, FRGS was confirmed as an independent prognostic factor after adjusted for TNM stage of tumor in multivariate analysis (Training cohort: HR = 3.19, 95%CI = 1.88-5.41, P&lt; 0.001; Validation-1 cohort: HR = 5.00, 95%CI = 1.58-15.85, P= 0.007; Validation-2 cohort: HR = 2.99, 95%CI = 1.44-6.21, P= 0.003). Furthermore, enrichment analysis found that anti-tumor immune response was suppressed in the high CAF risk group. Conclusions: The 11-gene FRGS had independent prognostic value for CRC patients, as well as in prediction of benefit from chemotherapy. CAF in tumor microenvironment might impact on the prognosis of CRC patients via inhibiting immune response.
Machine learning imputation of metastatic status from open claims in melanoma patients.
Authors: Vivek Prabhakar Vaidya, Rambaksh Prajapati, Sai Vinod Manirevu, Rohini George, Smita Agrawal, Babu Narayanan
Journal: Journal of Clinical Oncology (2021)

e21540 Background: Metastatic status is a crucial variable in most oncology studies but is not available in claims data. The objective of this study is to develop a machine learning model for Imputation of metastatic status from claims data with ground. Truth is derived from highly curated electronic medical record data. Methods: We used a set of 11389 melanoma patients from the ConcertAI real world database of intersecting claims and EMR data that includes data from CancerLinQ Discovery. Using features from claims and our gold standard labels from EMR we built an ML model using (XGBoost) extreme gradient boosting, an algorithm that iteratively combines a set of decision trees into a single model. We used 60% of the data for training, 20% for hyper-parameter tuning, and 20% for holdout testing. The model was built using 55 features. Results: The table below summarizes results. Metrics are on the final hold out set which was unseen by the model and entirely composed of highly curated EMR data. Conclusions: We are able to build a high precision model for the imputation of metastatic melanoma status using claims data. This could enable significantly better use of claims data stemming from the ability to find a metastatic cohort with very few false positives. Providing more precise cohort identification for comparative effectiveness studies. We found features such as secondary neoplasm diagnosis, anti-neoplastic meds, and radiation ranking highly in our analysis of model feature importances. Using techniques to analyze non-linear feature interactions in our AI model we found an interaction relationship between long term anti-neoplastic therapy, reported pain and metastatic status which we plan to further study. This work is preliminary and we are working to further improve model performance.[Table: see text]
Internal medicine residents’ awareness on cancer survivorship care plan: A cross sectional study.
Authors: Ivy Riano, Hugo Pomares-Millan, Klaorat Prasongdee, Robin Park, Narjust Duma
Journal: Journal of Clinical Oncology (2021)

e23011 Background: Survivorship care plans (SCPs) is recommended as a tool for communication between oncologists and primary care physicians. According to the Institute of Medicine, it is necessary to lead a cultural shift to provide SCPs to all cancer survivors to improve the transition from the oncology clinic to primary care practices. Studies suggest residency training curriculums for internal medicine (IM) are lacking education about cancer survivorship and SCPs. We aimed to assess the awareness of trainees toward SCPs. Methods: A survey was distributed to IM trainees in an outpatient setting. We stratified the descriptive analyses by program type (transitional [TY] and categorical [CT] trainees) and year of training. Differences in the proportions were tested appropriately. Analyses were conducted in R v3.6.2. Results: 37 trainees were interviewed; 32.4% were TY and 67.6% CT trainees. A 54% were PGY-1, 21.6% PGY-2, and 24.3% PGY-3. None of the trainees reported following a SCP for cancer-free patients nor to use SCP as a source to obtain cancer-related information. 78.3% and 92.6% reported that they were not taught during residency or medical school about SCPs, respectively. 84.8% informed that cancer-related information was inaccessible during the encounter with patients; sources cancer diagnosis and treatment information included: patients/family members (97.3%), outside records (83.8%), and oncology notes (86.5%). By program type, there was a statistically significant difference between TY v. CT groups (p = 0.017) regarding how often cancer-related issues were discussed with patients; the TY group mainly reported ‘Not at all’ whether CT were more likely to engage in discussion about cancer. Differences in the trainees’ comfort level answering patients concerns about cancer recurrence were observed between TY v. CT trainees but was not statistically significant (p = 0.864). Most common barriers to discuss cancer history and/or SCP were insufficient information from patients (83.8%), perceived inaccuracy from patients’ information (81.1%), unclear if patient has a SCP (81.1%), lack of SCP in medical record (75.7%), and trainees’ low medical knowledge about side effects of cancer therapies (70.3%). Conclusions: The awareness of cancer SCP among the IM trainees is limited, and many have not accessed or received training in SCPs. Efforts intended to facilitate SCP use and educate residents about cancer survivorship may be effective to increase the comfort level of trainees managing the growing number of survivors and improve transition from oncology to primary care clinics.[Table: see text]