tbuckley/cabot-search huggingface dataset:
THU0169 COMPARISON OF THE SYNOVIAL RESPONSE TO MECHANICAL STRESS AMONG PATIENTS WITH RHEUMATOID ARTHRITIS IN CLINICAL REMISSION ON METHOTREXATE OR ANTI-TNF
Authors: C. Guillén-Astete, P. Zurita-Prada, C. Urrego-Laurín
Journal: Annals of the Rheumatic Diseases (2020)

Background: Physiologically, the joint synovium responds to physical activity according to the frequency and intensity of the efforts, producing slight effusion without detectable hyperemia. In patients with RA in remission, a similar response can be expected, since it is understood that the immune-mediated inflammatory component has been controlled physiopathologically. Our interest is to determine whether once clinical remission has been reached, treatment with MTX or antiTNF produces the same normalization of the synovial behaviour. Our interest is to determine whether once clinical remission has been reached, treatment with MTX or antiTNF produces the same normalization of the synovial behavior. Objectives: The aim of the present study is to compare the synovial response to mechanical stress of patients with Rheumatoid Arthritis (RA) in remission treated with Methotrexate (MTX) or Etanercept (ETN). Methods: Descriptive observational study. We included patients with RA in remission (DAS28&lt;2.6) for at least 6 months on MTX or MTX and anti-TNF-alpha therapy (ETN). An ultrasound examination protocol was developed for the 2nd, 3rd and 4th MCP and non-dominant hand carpus for gray scale (GS) and power Doppler signal detection (sPD) according to EULAR/OMERACT definitions. Two ultrasound examinations were performed on each patient, before and 24 hours after starting a manual digital flexure exercise program against resistance measured by a handheld dynamometer CAMRY™ model EH101-17. Total synovitis scores in EG (0-12) and sPD (0-12) were compared. Results: We included 37 patients on MTX treatment (median dose 15mg/week, range 7.5-25mg/week) and 16 patients on ETN treatment (median dose 50mg/week, range 25-50 mg/week). The baseline ultrasound score in the MTX treatment group was 1.6 SD 1.4 in EG and 2.2 SD 0.5 in PDs. After carrying out the controlled dynamometric effort, the score was 2.4 SD 1.9 in GS and 4.4 SD 1.5 in PDs (P&lt;0.05 and P&lt;0.001, respectively). In patients treated with TNEs, the basal score in GS was 1.3 SD 0.6 in GS and 0.6 SD 0.3 in PDs. After the controlled dynamometric effort, the score was 1.8 DE 0.9 in EG and 0.7 DE 0.4 in PDs (P=0.07 and P&lt;0.001, respectively). In the group of patients treated with MTX, four subjects reported joint tenderness after physical effort. Conclusion: Our observations are congruent with previous experiences in which it has been observed that physical stress translates into synovial changes detectable by ultrasonographic studies. Our results, although modest in patient volume, suggest that TNF-alpha activity is crucial in the development and maintenance of exercise-induced hyperemia. The clinical significance of our observation may be useful as a tool to predict the response to anti-TNF therapy in patients with RA, however specific methodological designs are needed for such associations. Disclosure of Interests: None declared
Translating Targeted Temperature Management Trials into Postarrest Care
Authors: Laurie J. Morrison, Brent Thoma
Journal: New England Journal of Medicine (2021)

Scientific evidence is often poorly implemented or misinterpreted when it is incorporated into clinical practice.1 Trends in clinical care after publication of the first TTM (Target Temperature Management 33°C versus 36°C after Out-of-Hospital Cardiac Arrest) trial2 are illustrative and alarming. Aiming to build on remarkable improvements in outcomes in patients after cardiac arrest, the TTM trial used standardized surface or intravascular temperature-management protocols to test whether a targeted temperature of 33°C (hypothermia) was superior to a targeted temperature of 36°C (normothermia). It was not; mortality and neurologic outcomes were similar. After publication of the trial results, surveys from multiple countries . . .
Digital footprint of hematology-oncology fellowship programs: Identifying gaps after the first virtual recruitment season.
Authors: Ana I. Velazquez Manana, Inas Abuali, Juan J. Rodriguez Vargas, Minira Aslanova, Yaniris Molina Aponte, Yaideliz Romero Ramos, Narjust Duma
Journal: Journal of Clinical Oncology (2021)

11003 Background: The COVID-19 pandemic has led to unprecedented restrictions to travel and in-person activities that limit hematology/oncology (HO) fellowship programs’ (FP) recruitment activities. Prospective applicants rely on websites and social media (SOME) to guide their decisions of applying or ranking a FP. We aim to evaluate HO FP’s digital footprint in order to identify informational gaps. Methods: The AMA Fellowship and Residency Electronic Interactive Database (FREIDA) was queried for all HO programs. We searched Google, Twitter, Instagram, Facebook, and YouTube for HO FP pages. Content was evaluated using published criteria. Qualitative content analysis of SOME posts is planned. Results: Our analysis includes 176 FP that actively recruited during the 2020 match season. Over half (57%, n = 100) were university-based and the median number of fellow positions per year was 4 per FP (range 0-16). Most FP had websites (95%, n = 167) with varying information (Table) for prospective applicants. Twenty percent (n = 33) included a diversity statement. While 63% (n = 106) of FP provided application information, only 51% discussed visa requirements. Few FP websites included key information such as why fellows chose a particular FP (7%, n = 12), accolades of fellows (3%, n = 5), or employment location of alumni (25%, n = 44). Only 42% (n = 69) provided city, and 5% (n = 8) showed fellows socializing. Thirty-four FP (19%) have informational videos (range 1-10) in YouTube (length range: 1:37-18:15min). Most (82%; n = 28) were published since May 2020 in alignment with the FP recruitment season. Twitter was the second most common SOME platform, used by 19% (n = 32) of FP. 56% (n = 18) joined Twitter since May 2020 correlating with the current recruitment season. The number of Twitter followers (median 119, range: 0-1408) and posts (median 47, range: 0-687) varied across FP. Only 4% used Facebook and 6% Instagram. Conclusions: Our analysis of FP’s digital footprint revealed that applicants participating in the 1st virtual HO recruitment season were provided limited online information. Programs can use online content to provide information on resources, research opportunities, and achievements of faculty and fellows that can guide applicant decision making. In the era of COVID-19, highlighting the diversity and breath of each FP, hospital, and city are vital to attract a diverse and talented pool of trainees.[Table: see text]
Role of CD10 expression in endometriosis-associated mesenchymal stem cells on the progression of endometriosis-associated carcinoma.
Authors: Huda Atiya, Taylor Orellana, Lan Gardner Coffman
Journal: Journal of Clinical Oncology (2021)

5561 Background: Endometriosis-associated carcinomas (EACs) such as ovarian clear cell cancer (OCCC) are rare, aggressive, chemo-resistant malignancies. While endometriosis is a known chronic inflammatory condition, the molecular mechanisms for the malignant transformation of endometriosis is unknown. Mesenchymal stem cells (MSC) are a critical component of the ovarian cancer microenvironment. Cancer cells reprogram MSCs to form carcinoma-associated MSCs (CAMSCs), which promote cancer growth, chemotherapy resistance, and metastases. MSCs are also found within the endometriotic microenvironment. CD10, a surface protein expressed by endometrial stromal cells, is also expressed on endometriosis-associated MSCs (enMSCs). Preliminary data demonstrate CD10 expression is lost in a subset of enMSCs and this loss is correlated with the acquisition of tumor-promoting properties. We hypothesized that the CD10 negative subset of enMSCs behave similarly to CAMSCs and support the growth of OCCC. Methods: EnMSCs were isolated from primary human benign endometriosis deposits involving the ovary or fallopian tubes. Flow cytometry was used to measure surface CD10 expression. We investigated the role of low CD10 enMSCs versus high CD10 enMSCs on OCCC tumor cell growth, chemotherapy resistance and stem-like cell properties in vitro and tumor cell engraftment, growth, and metastases in vivo. Luciferase-expressing OCCC cells were (1) used alone, (2) mixed with low CD10 enMSCs, or (3) mixed with high CD10 enMSCs and injected orthotopically into the ovarian bursa of NSG mice. In vivo imaging system was used to follow tumor progression and metastasis. Results: Our results demonstrated that enMSCs have variable CD10 expression. EnMSCs with low CD10 expression significantly enhanced OCCC proliferation, resistance to cisplatin, and sphere formation compared to OCCC alone. In contrast, high CD10 expressing enMSCs significantly reduce OCCC proliferation and sphere formation. Interestingly, low CD10 enMSCs selectively enhanced OCCC cell growth and had no effect on high grade serious ovarian cancer cell growth. Moreover, a reduction of CD10 expression was observed over time when high CD10 enMSCs were co-cultured with OCCC cells. Our results also showed enhanced tumor engraftment when OCCC cells were co-injected with low CD10 enMSCs to 100% one week post-injection, compared to 40% with OCCC and high CD10 enMSCs and 60% with OCCC alone. Further, mice co-injected with low CD10 enMSCs demonstrated increased metastasis and decreased survival compared to mice co-injected with high CD10 enMSCs. Conclusions: Our results indicate there is a sub population of enMSCs, marked by decreased CD10 expression, which selectively enhances OCCC growth. This highlights the existence of a tumor-promoting stromal cell within endometriosis which may be critical to the formation and propagation of EACs.
Response and outcomes to immune checkpoint inhibitors (ICI) in advanced urothelial cancer (aUC) based on prior intravesical BCG.
Authors: Rafee Talukder, Dimitrios Makrakis, Daniel Castellano, Vadim S Koshkin, Ajjai Shivaram Alva, Tyler F. Stewart, Victor Sacristan Santos, Jayanshu Jain, Rafael Morales-Barrera, Michael Grant, Ariel Ann Nelson, Evan Shreck, Alexander Sankin, Roubini Zakopoulou, Alejo Rodriguez-Vida, Sandy Liu, Ana Fröbe, Giuseppe Di Lorenzo, Petros Grivas, Ali Raza Khaki
Journal: Journal of Clinical Oncology (2021)

4537 Background: Little is known regarding response and outcomes to ICI for patients (pts) with aUC who were previously treated with BCG for non-muscle invasive bladder cancer. We hypothesized that prior intravesical BCG would not be associated with changes in objective response or survival in pts with aUC treated with ICI. Methods: We performed a retrospective cohort study across 25 institutions. Demographic, intravesical BCG history, treatment and outcomes data were collected for pts with aUC who received ICI. Pts with aUC treated with ICIs were included, pts with pure non-UC, those treated with combination or on clinical trials, pts with multiple ICI treatment lines and those with upper tract UC were excluded. Pts were stratified to prior exposure versus no exposure to BCG. We compared overall response rate (ORR) using logistic regression; and progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier and Cox proportional hazards. All analyses were performed in the overall population and further stratified by treatment line (first-line [1L] vs salvage [2+L]) and multivariable models. The stratified analysis was also adjusted for an internally developed risk score for 1L and Bellmunt risk score for 2+L; p&lt;0.05 was significant. Results: 1026 aUC pts treated with ICI were identified; 614 pts, 617 pts, and 641 pts were included in ORR, OS and PFS analyses, respectively. Overall, mean age at CPI initiation was 70, 76% were men, 70% were current or former smokers, 75% White, 29% with mixed histology, and 24% had prior exposure to BCG. ORR to ICI in pts with or without prior exposure to BCG was similar, 27% and 28% respectively (OR=0.93 [95% CI 0.61-1.42], p=0.73). Median OS (mOS) for pts with vs without prior BCG exposure was 9 vs 10 mo (HR=1.13 [95% CI 0.88-1.44], p=0.35). Median PFS (mPFS) was 4 months (mo) in both groups (HR=1.02 [95% CI 0.82-1.27], p=0.83). ORR, PFS and OS analyses stratified by ICI treatment line (1L vs 2+L) are listed in the table. Conclusions: In this multi-institutional retrospective analysis, prior intravesical BCG was not associated with objective response or survival in pts with aUC treated with ICI. Limitations of this study include retrospective nature, lack of randomization and possible confounding, but it does provide important preliminary data that selection for ICI treatment should not be impacted by prior exposure to BCG. Further clinical and molecular biomarker exploration is needed to refine patient selection for ICI in aUC.[Table: see text]
A natural language processing tool for automatic identification of new disease and disease progression: Parsing text in multi-institutional radiology reports to facilitate clinical trial eligibility screening.
Authors: Eric J. Clayton, Imon Banerjee, Patrick J. Ward, Maggie D Howell, Beth Lohmueller, Sunita Pierson, Rachel Hall, Peter B Harrison, David Michael Waterhouse
Journal: Journal of Clinical Oncology (2021)

1555 Background: Screening every patient for clinical trials is time-consuming, costly and inefficient. Developing an automated method for identifying patients who have potential disease progression, at the point where the practice first receives their radiology reports, but prior to the patient’s office visit, would greatly increase the efficiency of clinical trial operations and likely result in more patients being offered trial opportunities. Methods: Using Natural Language Processing (NLP) methodology, we developed a text parsing algorithm to automatically extract information about potential new disease or disease progression from multi-institutional, free-text radiology reports (CT, PET, bone scan, MRI or x-ray). We combined semantic dictionary mapping and machine learning techniques to normalize the linguistic and formatting variations in the text, training the XGBoost model particularly to achieve a high precision and accuracy to satisfy clinical trial screening requirements. In order to be comprehensive, we enhanced the model vocabulary using a multi-institutional dataset which includes reports from two academic institutions. Results: A dataset of 732 de-identified radiology reports were curated (two MDs agreed on potential new disease/dz progression vs stable) and the model was repeatedly re-trained for each fold where the folds were randomly selected. The final model achieved consistent precision (&gt;0.87 precision) and accuracy (&gt;0.87 accuracy). See the table for a summary of the results, by radiology report type. We are continuing work on the model to validate accuracy and precision using a new and unique set of reports. Conclusions: NLP systems can be used to identify patients who potentially have suffered new disease or disease progression and reduce the human effort in screening or clinical trials. Efforts are ongoing to integrate the NLP process into existing EHR reporting. New imaging reports sent via interface to the EHR will be extracted daily using a database query and will be provided via secure electronic transport to the NLP system. Patients with higher likelihood of disease progression will be automatically identified, and their reports routed to the clinical trials office for clinical trial screening parallel to physician EHR mailbox reporting. The over-arching goal of the project is to increase clinical trial enrollment. 5-fold cross-validation performance of the NLP model in terms of accuracy, precision and recall averaged across all the folds.[Table: see text]
OMIC-13. THE ROLE OF COPY NUMBER ALTERATIONS IN PREDICTING SURVIVAL AND INFLUENCING TREATMENT OF CHILDHOOD BRAIN TUMORS
Authors: Sharon Freshour, Bryan Fisk, Christopher Miller, Obi Griffith, Malachi Griffith, Joshua Rubin
Journal: Neuro-Oncology (2021)

Abstract Brain and central nervous system tumors are the most common form of solid tumor cancers and the second most common cancer overall among children. While many advances have been made in understanding the genomics of childhood brain tumors in recent years, the role of copy number alterations (CNAs) has not been fully characterized. Although the genomes of childhood brain tumor patients are generally considered to be relatively stable diploid genomes, analysis of a subset of pretreatment diagnostic samples from a cohort of 84 deceased patients from Washington University revealed widespread alterations, suggesting CNAs may play a larger role in the progression and prognosis of childhood brain tumors than originally thought. Follow up analysis of the entire cohort, containing a variety of tumor types that had low-pass whole genome sequencing performed, similarly showed evidence of CNAs across samples. 75 out 84 patients showed the presence of CNAs with an average of 16% of the genome being altered per sample and a median of 7%. Preliminary results examining correlations between the percentage of the genome that was copy number altered and event free survival or overall survival indicated that CNA percentage may have some prognostic value. For example, ependymoma samples showed positive correlation between alteration percentage and overall survival, while glioblastoma samples showed negative correlation. To explore copy number alteration in a larger cohort and increase statistical power, similar analyses are being performed using an additional 950 samples from the Pediatric Brain Tumor Atlas curated by The Children’s Brain Tumor Network (CBTN) to determine if CNVs and CNV percentage or specific alterations can serve as prognostic markers and whether the biology of this genomic instability could inform therapeutic strategy.
BDB001, an intravenously administered toll-like receptor 7 and 8 (TLR7/8) agonist, in combination with pembrolizumab in advanced solid tumors: Phase 1 safety and efficacy results.
Authors: Manish R. Patel, Anthony W. Tolcher, Drew W. Rasco, Melissa Lynne Johnson, Angela Tatiana Alistar, Lixin Li, Alexander H. Chung, Robert H.I. Andtbacka
Journal: Journal of Clinical Oncology (2021)

2512 Background: BDB001 is an intravenously administered TLR 7/8 dual agonist immune modulator capable of reprogramming dendritic cells to produce antitumor activities. BDB001 monotherapy has demonstrated favorable tolerability and robust systemic immune activation leading to durable clinical responses in a phase I dose escalation trial. Here, we report on the safety and efficacy of BDB001 in combination with pembrolizumab in a phase I dose escalation trial in advanced solid tumors (NCT03486301). Methods: BDB001-101 is a phase 1, open label, dose escalation/expansion trial of BDB001 (IV, Q1W) in combination with pembrolizumab (IV, Q3W) in patients with advanced solid tumors. The primary endpoint was safety and tolerability. Secondary endpoints included efficacy, pharmacokinetics and pharmacodynamic profiling of immune activation. Results: Twenty-three subjects with 13 different tumor types were enrolled across 4 dose levels. Sixty one percent were female, median age was 63 years (range, 33-86), median number of prior therapies was 3 (range, 1-8), and 48% of tumors had progressed on prior anti-PD-(L)1 therapy. Overall, BDB001 in combination with pembrolizumab was well tolerated and dose-limiting toxicities were not observed. The most common treatment related adverse events (TRAEs) were fever (39.1%), fatigue (39.1%), chills/rigor (34.8%), pruritus/rash (21.7%), and nausea (13.0%). Most of these TRAEs were grade 1 or 2 and transient. Only 3 (13.0%) subjects experienced grade 3 TRAEs of fatigue, rash, stomatitis, and alkaline phosphatase elevation. There were no grade 4 or 5 TRAEs. Pharmacodynamic evaluation of plasma cytokine levels showed robust increases in interferon gamma and interferon inducible protein-10 (IP-10) at BDB001 Dose Level 3 and 4. Preliminary efficacy evaluation of the 14 subjects treated at Dose Level 3 and 4 showed durable and deep clinical responses in 4 (29%) subjects with anti-PD-(L)1 mAb refractory melanoma, hepatocellular carcinoma, cholangiocarcinoma, and platinum-resistant ovarian carcinoma. The responses were observed by the initial efficacy assessment at 9-weeks, with some seen as early as 4-weeks. In addition, 4 (29%) subjects had stable disease for a disease control rate of 57%. To date, median time on treatment is 14.4 weeks (range, 6.0 – 42.1+) with 3 subjects still active on treatment. Conclusions: Intravenously administered BDB001 in combination with pembrolizumab is well tolerated. Rapid and deep clinical responses were observed, supported by robust systemic immune activation. BDB001 in combination with pembrolizumab is a promising novel therapeutic option for patients with advanced solid tumors and is being evaluated in an ongoing dose expansion trial. Clinical trial information: NCT03486301.
Therapy-related myeloid neoplasms following treatment with PARP inhibitors: new molecular insights
Authors: J.E. Martin, S. Khalife-Hachem, T. Grinda, M. Kfoury, S. Garciaz, F. Pasquier, J. Vargaftig, M. Uzunov, A. Belhabri, S. Bertoli, S. Cotteret, V. Vergé, A. Renneville, F. Rosselli, I. Antony-Debre, E. Rouleau, F. Salviat, O. Caron, S. Delaloge, P. Pautier, G. Etienne, C. Recher, N. Vey, S. De Botton, A. Leary, C. Marzac, J.B. Micol
Journal: Annals of Oncology (2021)