tbuckley/cabot-search huggingface dataset:
Outcomes in the dedifferentiated liposarcoma cohort of SAR-096, a phase II trial of ribociclib in combination with everolimus in advanced dedifferentiated liposarcoma (DDL), and leiomyosarcoma (LMS).
Authors: Margaret von Mehren, Sujana Movva, Elizabeth A. Handorf, Priscilla Merriam, Jeffrey A. Morgan, Edwin Choy, Eric Daniel Tetzlaff, Emma Barker, Allisa Cherae Harley, April King, Sahar Matloob, Erika Jerome, Lori Rink, Suzanne George
Journal: Journal of Clinical Oncology (2021)

11515 Background: Dedifferentiated liposarcoma (DDL) is characterized by ring chromosomes of chromosone12, which includes amplification of MDM2 and CDK4. Exposure to CDK4 inhibitors in Rb+ leiomyosarcoma (LMS) cell lines leads to decreased cell proliferation, and increased senescence, and G0/G1-phase arrest. When combined, ribociclib a CDK4 inhibitor and everolimus, an mTOR inhibitor show synergistic growth inhibition in multiple tumor models. We hypothesized that this combination could lead to increased disease control in patients with DDL. Methods: This study enrolled patients (pts) into one of two cohorts: DDL or Rb+ LMS. LMS pts were required to have 1 prior line of therapy; DDL pts required no prior therapy. There were no limits to prior therapies in either group. Measurable disease by RECIST 1.1 was also required. Ribociclib was given at 300 mg daily for 21/28 days and everolimus was given continuously at 2.5 mg daily in 28 day cycles. The primary endpoint was progression free rate at 16 weeks. A Simon two-stage design was utilized and if at least 8 out of 24 pts were progression free at 16 weeks, the treatment was declared promising for the cohort. Here in we present data on the DDL cohort. Results: To date, 21 DDS pts, median age of 63 (range 40-79), of which 43% (n = 9) female were treated. Median prior lines of therapy was 1 (range 0-6). Of 19 pts with complete data, 8 (42%) met the primary endpoint of non-progression at 16 weeks. Confirmed partial response was seen in 2 pts (10%). Median PFS was 16 weeks, and stable disease occurring as best response in 11 (55%) pts. Grade 3-4 toxicities were uncommon except for lymphopenia (24%) and neutropenia (33%); no episode of neutropenic fever were observed. There was one death on study secondary to myocardial infarction, considered possibly related to therapy. Results of optional tissue biopsies pre and on therapy obtained to assess pharmacodynamic changes in PTEN, pAKT, CDK4, Rb and pS6 will be presented. Conclusions: The combination of ribociclib and everolimus demonstrates activity in DDL with prolonged stable disease (&gt;16 weeks) meeting the primary protocol endpoint. Notably partial responses were also observed. The combination was well tolerated with acceptable side effects. Updated outcomes will be presented. Clinical trial information: NCT03114527.
Aminergic status in the brain of urokinase gene-deficient mice with malignant tumors growing in presence of chronic neurogenic pain.
Authors: Yulia A. Pogorelova, Irina V. Kaplieva, Elena M. Frantsiyants, Ekaterina I. Surikova, Valeria A. Bandovkina, Irina V. Neskubina, Natalia D. Cheryarina, Elena V. Shalashnaya, Polina S. Kachesova, Ludmila A. Nemashkalova, Oleg I. Kit, Viktoria V. Pozdnyakova
Journal: Journal of Clinical Oncology (2021)

e21582 Background: The fibrinolytic system of the brain is important for its normal functioning and participation in processes that are significant in various stressful influences, including tumor growth and chronic neurogenic pain (CNP). These pathological conditions change the activity of the brain neurotransmitter system. On the other hand, urokinase deficiency is associated with significant inhibition of tumor growth, while CNP – with its stimulation. The purpose of the study was to analyze the effect of CNP on the levels of biogenic amines in the brain of mice with urokinase deficiency (uPA-/-) with transplanted B16/F10 melanoma. Methods: The study included male and female mice: С57ВL/6 (uPA+/+, n = 48) and C57BL/6-Plautm1.1Bug-ThisPlauGFDhu/GFDhu (urokinase gene-knockout - uPA-/-, n = 48). Mouse strains were divided into subgroups (each n = 6): intact; with CNP (bilateral sciatic nerve ligation); 21 days after subcutaneous transplantation of B16/F10 melanoma; 21 days of B16/F10 melanoma growth in presence of CNP (B16/F10+CNP), with tumor transplantation 2 weeks after the sciatic nerve ligation. Levels of adrenaline (A), noradrenaline (NA), dopamine (DA), histamine, serotonin (5HT), and 5-hydroxyindoleacetic acid (5OHIA) were determined in the brain by ELISA (Cusabio, China). Statistical processing - Statistica 10.0. Results: Levels of NA, DA and 5HT in the brain of intact uPA-/- mice were 3.5, 2.1 and 1.9 times higher (p &lt; 0.05), respectively, than in intact uPA+/+ animals, while histamine and 5OHIA were on average 2.0 times lower. The dynamics of cerebral levels of biogenic amines in uPA-/- mice with pathological factors, alone or combined, had practically no gender specificity, with rare exceptions. So, 5HT levels increased up to 4.5 times in uPA-/- mice of both sexes in response to CNP or B16/F10 growth. Melanoma growth in presence of CNP, on the contrary, decreased 5HT by 3-10 times and DA by 1.6 times (p &lt; 0.05) both in males and females, and decreased NA by 1.6 times (p &lt; 0.05) in females. Conclusions: CNP together with melanoma inhibits the initial activation of the HA-, DA- and 5HT-ergic systems in the brain of uPA-/- mice, which may be an important pathogenetic mechanism of the cancellation of genetically determined inhibition of subcutaneous B16/F10 melanoma growth in urokinase deficiency.
Self-reported gender bias encountered by hematology and oncology fellows.
Authors: Nino Balanchivadze, Karla D. Passalacqua, Sally Askar, Philip Kuriakose, Narjust Duma, Vinod E. Nambudiri, Kylie Springer, George Divine, Vijayalakshmi Donthireddy
Journal: Journal of Clinical Oncology (2021)

11017 Background: Gender-related bias and discrimination have been well documented, particularly in male-dominated fields such as surgery, and have been associated with increased risk for physician burnout. In hematology/medical oncology, women make up between 41% and 49% of first-year fellows, but represent less than 40% of the academic hematology/oncology workforce. We aimed to study current hematology/oncology fellow perceptions about gender-related bias and challenges to inform interventions that promote gender equity. Methods: An anonymous 18-question survey was sent online to 165 adult and 75 pediatric hematology/oncology fellowship programs. Two group comparisons to analyze survey responses between genders were performed using chi-square, or Fisher’s test (if cell counts &lt; 5), and Wilcoxon Rank Sum tests. Results: A total of 133 fellows completed the survey, where 88 self-identified as female (66%) and 45 (33.83%) self-identified as male. Most participants were White (52%), followed by Asian (29%), Hispanic (9%), Middle Eastern (5%), and Black (3%). Most respondents (n = 100; 75%) were age 31-40 years. More than half (54%) were enrolled in adult hematology/oncology fellowships, 24% were enrolled in pediatric hematology/oncology fellowship programs, and 88% practiced in University-based programs. Compared to male respondents, female fellows were more likely to report experiencing gender bias (p &lt; 0.001), felt more insecure in their job (p = 0.043), felt second-guessed by colleagues (p &lt; 0.001), and were more likely to believe that they had been unfairly denied a promotion (p = 0.003). In addition, female respondents were more likely to report having been mistaken as a non-physician (p &lt; 0.001) and were more concerned about perceived gender bias. Female respondents reporting gender bias used techniques such as wearing a white coat (p &lt; 0.0001), emphasizing a professional look (p &lt; 0.0001), and ensuring “Doctor” (p &lt; 0.0001) was clearly written on their badge more often than male fellows. When asked about how to combat gender-related challenges, female fellows more often recommended formal lectures and instruction about gender bias for attending physicians and non-physician staff. Suggestions about mitigating gender-related bias included encouraging same-sex mentors and open discussions about existing bias. Conclusions: Female hematology/oncology fellows reported facing gender-related bias and challenges in daily practice and often used specific techniques to face these challenges. Transparency and directed education about gender bias may help mitigate these challenges to create better working environments for fellows.
Genetics of Sleep and Insights into Its Relationship with Obesity
Authors: Hassan S. Dashti, José M. Ordovás
Journal: Annual Review of Nutrition (2021)

Considerable recent advancements in elucidating the genetic architecture of sleep traits and sleep disorders may provide insight into the relationship between sleep and obesity. Despite the involvement of the circadian clock in sleep and metabolism, few shared genes, including FTO, were implicated in genome-wide association studies (GWASs) of sleep and obesity. Polygenic scores composed of signals from GWASs of sleep traits show largely null associations with obesity, suggesting lead variants are unique to sleep. Modest genome-wide genetic correlations are observed between many sleep traits and obesity and are largest for snoring. Notably, U-shaped positive genetic correlations with body mass index (BMI) exist for both short and long sleep durations. Findings from Mendelian randomization suggest robust causal effects of insomnia on higher BMI and, conversely, of higher BMI on snoring and daytime sleepiness. In addition, bidirectional effects between sleep duration and daytime napping with obesity may also exist. Limited gene-sleep interaction studies suggest that achieving favorable sleep, as part of a healthy lifestyle, may attenuate genetic predisposition to obesity,but whether these improvements produce clinically meaningful reductions in obesity risk remains unclear. Investigations of the genetic link between sleep and obesity for sleep disorders other than insomnia and in populations of non-European ancestry are currently limited.
Absolute Monocyte Count at Diagnosis Could Improve the Prognostic Role of Final FDG-PET in Diffuse Large B Cell Lymphoma Patients
Authors: Raffaella Marcheselli, Antonella Franceschetto, Alessia Bari, Luigi Marcheselli, Tamar Tadmor, Samantha Pozzi, Ilana Levy, Patrizia Pizzichini, Daniela Prosperi, Maria Christina Cox, Rosaria D'Apollo, Lucia Massi, Napoleone Prandini, Stefano Sacchi
Journal: Blood (2017)
A phase 1 study of SGN-B6A, an antibody-drug conjugate targeting integrin beta-6, in patients with advanced solid tumors (SGNB6A-001, Trial in Progress).
Authors: Amita Patnaik, Emiliano Calvo, Sarina Anne Anne Piha-Paul, Antoine Hollebecque, Vladimir Galvao, Juanita Suzanne Lopez, Fadi S. Braiteh, Rachel E. Sanborn, Peigen Zhou, Natalya N. Nazarenko, Afshin Dowlati
Journal: Journal of Clinical Oncology (2021)

TPS3144 Background: The extracellular matrix (ECM) plays an important role in solid tumor pathogenesis and is a major focus of research and therapeutic targeting. Integrin beta-6 is a cell surface receptor that interacts with the ECM to mediate cellular adhesion. Integrin beta-6 is overexpressed in numerous solid tumors and its expression is a negative prognostic marker in cancers including colorectal, non-small cell lung, gastric, and cervical cancers. SGN-B6A is an investigational vedotin, an antibody-drug conjugate directed against integrin beta-6 to selectively deliver the cytotoxic agent monomethyl auristatin E, which binds tubulin and induces apoptosis. In multiple xenograft models, treatment with SGN-B6A resulted in tumor growth delay and regression in tumor volume when compared to non-binding control. Methods: SGNB6A-001 (NCT04389632) is a phase 1, first-in-human, open-label, multicenter study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and antitumor activity of SGN-B6A in adults with select advanced solid tumors. Primary objectives are to evaluate the safety and tolerability of SGN-B6A in patients with advanced solid tumors, identify the maximum tolerated dose, and identify a recommended dose and schedule. The study has 2 parts: dose escalation (Part A) and dose expansion with multiple disease-specific cohorts and a biology cohort (Part B). SGN-B6A will initially be given by intravenous infusion on Days 1, 8, and 15 of 21-day cycles. The dose escalation (Part A) will be conducted using the modified toxicity probability interval method to determine a dose that demonstrates a dose-limiting toxicity rate of 25% with a 5% margin. The dose and schedule for Part B will be determined based on evaluation of safety, PK, and pharmacodynamic biomarkers. Response evaluations will be based on RECIST v1.1. Patients must be ≥18 years old and have histologically or cytologically confirmed metastatic or unresectable solid malignancy within one of the following tumor types: non-small cell lung cancer, head and neck squamous cell cancer, breast cancer, esophageal cancer, ovarian cancer, cutaneous squamous cell cancer, exocrine pancreatic adenocarcinoma, bladder cancer, cervical cancer, or gastric cancer. After an appropriate dose and schedule are determined in Part A, safety and preliminary antitumor efficacy of SGN-B6A will be evaluated in indication-specific cohorts (Part B). This study is ongoing in sites across North America and Europe. Clinical trial information: NCT04389632.
Outcome disparities in rural versus urban patients with head and neck cancer: Leveling the playing field.
Authors: Varinder Kaur, Anthony Rooney, Raj Piyush Desai
Journal: Journal of Clinical Oncology (2021)

e18529 Background: Multiple studies indicate that rural patients experience disproportionately adverse cancer related outcomes, compared to their urban counterparts. This has been attributed to inequities in access to healthcare, monetary and technological resources, disease characteristics, adverse health status and lower life expectancy of rural populace. Whether treating patients with uniform protocols can help mitigate outcome disparities remains to be determined. Methods: We conducted a retrospective cohort study to evaluate survival outcomes of Head-Neck Squamous Cell Cancer (HNSCC) patients from rural versus urban locales. Only patients with locally advanced HNSCC who completed radiotherapy (RT) at the Emily Couric Clinical Cancer Center were included. Rural patients had access to affordable lodging for the duration of radiotherapy (RT), were treated regardless of health insurance status and by the same multidisciplinary team. Patients with distant metastases were excluded. Patients were classified as urban or rural using the Rural-Urban Commuting Areas (RUCA) zip-code database. Overall survival (OS) was analyzed using Kaplan-Meier curves and log-rank test. OS was modeled with a COX proportional hazards model, adjusting for several covariates including race, age, gender, HPV status, smoking, treatment received (RT, chemotherapy, surgery) and stage. Results: 230 patients with Stage I-IVB HNSCC who met the inclusion criteria were analyzed, of which 136 were categorized as residentially urban and 94 were categorized as rural. Approximately 83% were male, 87% were Caucasian and 71% were smokers (52% current smokers and 19% former smokers). In addition to RT, 42% patients had undergone surgery and 57% received chemotherapy. There was no statistically significant difference in OS for patients residing in rural vs urban zip-codes (HR 1.36, p = 0.24). Rural patients were less likely to undergo surgery (34% vs 44%, p = 0.04), and more likely to receive chemotherapy (67% vs 54%, p = 0.0325), likely indicating more advanced tumor stage at diagnosis. Conclusions: Rural and urban patients had similar OS when treated with similar treatment protocols. Improving access to uniform treatment regimens may help mitigate the widening gap in cancer-related outcomes between rural and urban populations.
Role of chest radiation in extensive-stage small cell lung cancer with ipsilateral pleural effusion.
Authors: Takefumi Komiya, Emily Powell, Charles Vu, Shinkichi Takamori
Journal: Journal of Clinical Oncology (2021)

e20567 Background: Prognosis of extensive-stage small cell lung cancer (ES-SCLC) remains poor. Previous randomized trials suggested consolidation chest radiation (CXRT) has a modest survival benefit; however, its role in subgroups of ES-SCLC, especially ipsilateral pleural effusion (IPE) have not been reported and unknown. Methods: Using National Cancer Database (NCDB), 283,347 ES-SCLC cases diagnosed between 2004 and 2017 were screened. Eligible cases must have been staged with 7 th edition of staging system and have information about clinical T and N stage, and minimum follow-up of one month. Role of CXRT was examined in M1a, M1b, and IPE subgroups. Surveillance, Epidemiology, and End Results Program (SEER) was analyzed to independently validate our results. Univariate and multivariate analyses were conducted with Cox proportional hazard models. A p-value &lt; 0.05 was considered as statistically significant. Results: A total of 36,762 (5,511 with M1a, 31,251 with M1b, and 2,013 with IPE) cases were analyzed. In both M1a and IPE groups, use of CXRT was significantly associated with younger age, female sex, non-academic institution, and clinical T stage. Both univariate and multivariate analyses showed that use of CXRT demonstrated significantly longer overall survival in all the groups, with lower hazard ratios in the M1a and IPE groups than in the M1b group (univariate hazard ratio 0.62, 0.56, and 0.72, respectively). Propensity score analysis of the IPE group also showed a survival advantage in the CXRT group (hazard ratio 0.54). The SEER data also showed a survival advantage of CXRT in the IPE group (univariate hazard ratio of 0.40). Conclusions: This retrospective database analysis suggests M1a and in particular IPE subgroups have more survival benefit of CXRT than the M1b subgroup. Further studies are warranted to confirm the hypothesis.
Temporal characteristics of treatment-emergent adverse events and dose modifications with tivozanib and sorafenib in the phase 3 TIVO-3 study of relapsed or refractory mRCC.
Authors: Sumanta K. Pal, David F. McDermott, Bernard Escudier, Thomas E. Hutson, Camillo Porta, Elena Verzoni, Michael B. Atkins, Michael N. Needle, Brian I. Rini
Journal: Journal of Clinical Oncology (2021)

4567 Background: The randomized phase 3 TIVO-3 study met the primary endpoint of improved PFS with tivozanib (TIVO) vs sorafenib (SOR) in patients with relapsed/refractory mRCC with fewer dose reductions, interruptions and discontinuations despite a longer time on therapy. Greater insight into temporal characteristics of treatment-emergent adverse events (TEAEs) may enable proactive supportive care strategies and improve patient experience. Methods: Updated safety from the previously reported TIVO-3 study with a data cutoff August 15, 2019, was analyzed by treatment arm for time-to-onset (TTO, days [d]) of the most commonly reported TEAEs, and TTO of first dose reduction, interruption, and discontinuation occurring with TIVO and SOR. Duration of TEAE (median d and IQ range), and rate of dose reduction, interruption, or discontinuation due to the TEAE was calculated for each arm. Results: Patients in the safety analysis randomly assigned to TIVO (n = 173) or SOR (n = 170) received 11.9 and 6.7 cycles, or 336 and 192 mean days of treatment exposure, respectively. Incidence of any Gr, Gr &gt;3, and TTO of any Gr TEAE of special interest occurring with &gt;20% frequency in either arm is shown in Table 1. While TIVO was associated with less Gr&gt;3 diarrhea, rash and PPE and more HTN than SOR, there were few differences in the TTO or duration of these TEAEs. Overall, dose reductions, interruptions, and discontinuations due to TEAEs were less frequent with TIVO than SOR, and TTO of first dose reduction (85 vs 45 d), interruption (81 vs 50 d), and discontinuation (114 vs 49 d) was longer for TIVO than SOR. Among those experiencing the same TEAE in either arm, resulting dose modifications were less frequent with TIVO than SOR. Conclusions: TIVO-3 demonstrated improved PFS with TIVO compared to SOR in mRCC, with longer duration of TIVO exposure, but fewer all Gr and Gr &gt;3 TEAEs. Temporal characteristics of TEAEs were similar, but time to dose modifications was longer with TIVO than SOR. Among those with the same TEAEs, unmodified treatment was continued more often with TIVO than SOR. Clinical trial information: NCT02627963. [Table: see text]
Leveraging Machine Learning and Artificial Intelligence to Improve Peripheral Artery Disease Detection, Treatment, and Outcomes
Authors: Alyssa M. Flores, Falen Demsas, Nicholas J. Leeper, Elsie Gyang Ross
Journal: Circulation Research (2021)

Peripheral artery disease is an atherosclerotic disorder which, when present, portends poor patient outcomes. Low diagnosis rates perpetuate poor management, leading to limb loss and excess rates of cardiovascular morbidity and death. Machine learning algorithms and artificially intelligent systems have shown great promise in application to many areas in health care, such as accurately detecting disease, predicting patient outcomes, and automating image interpretation. Although the application of these technologies to peripheral artery disease are in their infancy, their promises are tremendous. In this review, we provide an introduction to important concepts in the fields of machine learning and artificial intelligence, detail the current state of how these technologies have been applied to peripheral artery disease, and discuss potential areas for future care enhancement with advanced analytics.
Impact of self-reported environmental mould exposure on COPD outcomes
Authors: C. Kosmidis, R. Hashad, A.G. Mathioudakis, T. McCahery, M.D. Richardson, J. Vestbo
Journal: Pulmonology (2021)

Indoor and outdoor mould exposure can affect respiratory symptoms, but its contribution to COPD outcomes such as exacerbation rates or antibiotics courses is not well defined. Some patients with COPD develop chronic pulmonary aspergillosis (CPA), but the contribution of environmental exposure is not known.We correlated activities or exposures related to mould with COPD outcomes in patients with COPD with or without CPA using a questionnaire.One hundred and forty patients were included and 60 had CPA in addition to COPD. Seventy-six were male and mean age was 66.9 years (range 40-87). Thirty-nine (28%) were active cigarette smokers. On multivariate analysis, occupational contact with agricultural resources (p = 0.017), vacuuming once weekly or more often (p = 0.026) and not asking visitors to remove shoes on home entry (p = 0.035) were significantly more common in participants reporting ≥ 4 office visits for COPD symptoms in the last year. Living within one mile of industrial composting sites (p = 0.013), vacuuming once weekly or more often (p = 0.016) and not asking visitors to remove shoes on home entry (p = 0.028) were significantly more common in participants reporting ≥4 antibiotics courses in the last year. Patients with CPA showed a trend for residence within one mile of farms or agricultural areas (P = 0.088, OR 2, 95% CI 0.9-4.4).Activities potentially leading to mould exposure were common in a population with COPD with or without CPA and were associated with adverse COPD outcomes. Environmental mould exposure may play a role in the development of CPA in patients with COPD.