tbuckley/cabot-search huggingface dataset:
154TiP AdvanTIG-204: Anti-TIGIT monoclonal antibody (mAb) ociperlimab (OCI) plus anti-PD-1 mAb tislelizumab (TIS) plus concurrent chemoradiotherapy (cCRT) in patients (pts) with untreated limited-stage small cell lung cancer (LS-SCLC)
Authors: Y. Lu, Y. Gong, J-H. Kang, J. Whan Ree, X. Chen, X. Lin, J. Zhang, H. Borghaei
Journal: Annals of Oncology (2022)
Abstract EP30: Trends In Use Of Single Pill Combination Antihypertensive Medications And Blood Pressure Control In U.S. Adults With Hypertension
Authors: Claire Mobley, Alexis Bryan, Andrew E Moran, Catherine G Derington, Yiyi Zhang, Brandon K Bellows
Journal: Circulation (2022)

Background: Use of single pill combination (SPC) antihypertensive medications is associated with improved medication adherence and blood pressure (BP) outcomes compared with combinations of the same medications and doses taken as separate pills. We analyzed time trends of SPC use and BP control among US adults taking multiple antihypertensive medications and identified factors associated with SPC use. Methods: Combining National Health and Nutrition Examination Survey (NHANES) data from 2009-2018, we included participants aged &gt;=20 years with hypertension and taking &gt;=2 antihypertensive medications. Number of antihypertensive medications and SPC use were identified from self-reported prescription medications. Controlled BP was defined as systolic BP &lt;140 mm Hg and diastolic BP &lt;90 mm Hg. The age-adjusted proportion of individuals using SPC medications and BP control were estimated across each NHANES cycle. Multivariable logistic regression was used to assess trends in SPC use, BP control, and factors associated with SPC use. All estimates accounted for the complex survey design and represented the US population. Findings: Overall, 5,365 NHANES participants were included; mean (SD) age was 63.9 (12.0) years and 53.0% were female. SPC antihypertensive medication use decreased from 38.2% in 2009-2010 to 28.8% in 2017-2018 ( Figure , p=0.01). Similarly, BP control decreased from 72.1% in 2009-2010 to 64.4% in 2017-2018 (p=0.01). Age, male sex, body mass index, concurrent use of lipid-lowering therapy, and history of cardiovascular disease were significantly associated with decreased odds of SPC use. Conclusions: In the last decade, use of SPC antihypertensive medications and BP control each have decreased significantly among US adults taking &gt;=2 antihypertensive medications. Randomized trial evidence supports SPCs over separate pill combinations to improve BP outcomes. Efforts should be made to increase SPC use in targeted populations (e.g., those with comorbidities or polypharmacy).
Neoadjuvant Chemotherapy Induces Genomic and Transcriptomic Changes in Ovarian Cancer
Authors: Melissa Javellana, Mark A. Eckert, Janna Heide, Katarzyna Zawieracz, Melanie Weigert, Sarah Ashley, Elizabeth Stock, David Chapel, Lei Huang, S. Diane Yamada, Ahmed Ashour Ahmed, Ricardo R. Lastra, Mengjie Chen, Ernst Lengyel
Journal: Cancer Research (2021)

The growing use of neoadjuvant chemotherapy to treat advanced stage high-grade serous ovarian cancer (HGSOC) creates an opportunity to better understand chemotherapy-induced mutational and gene expression changes. Here we performed a cohort study including 34 patients with advanced stage IIIC or IV HGSOC to assess changes in the tumor genome and transcriptome in women receiving neoadjuvant chemotherapy. RNA sequencing and panel DNA sequencing of 596 cancer-related genes was performed on paired formalin-fixed paraffin-embedded specimens collected before and after chemotherapy, and differentially expressed genes (DEG) and copy-number variations (CNV) in pre- and post-chemotherapy samples were identified. Following tissue and sequencing quality control, the final patient cohort consisted of 32 paired DNA and 20 paired RNA samples. Genomic analysis of paired samples did not reveal any recurrent chemotherapy-induced mutations. Gene expression analyses found that most DEGs were upregulated by chemotherapy, primarily in the chemotherapy-resistant specimens. AP-1 transcription factor family genes (FOS, FOSB, FRA-1) were particularly upregulated in chemotherapy-resistant samples. CNV analysis identified recurrent 11q23.1 amplification, which encompasses SIK2. In vitro, combined treatment with AP-1 or SIK2 inhibitors with carboplatin or paclitaxel demonstrated synergistic effects. These data suggest that AP-1 activity and SIK2 copy-number amplification are induced by chemotherapy and may represent mechanisms by which chemotherapy resistance evolves in HGSOC. AP-1 and SIK2 are druggable targets with available small molecule inhibitors and represent potential targets to circumvent chemotherapy resistance. SIGNIFICANCE: Genomic and transcriptomic analyses identify increased AP-1 activity and SIK2 copy-number amplifications in resistant ovarian cancer following neoadjuvant chemotherapy, uncovering synergistic effects of AP-1 and SIK2 inhibitors with chemotherapy.
Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor–Expressing Salivary Gland Cancer: A Phase II Trial
Authors: Laura D. Locati, Stefano Cavalieri, Cristiana Bergamini, Carlo Resteghini, Elena Colombo, Giuseppina Calareso, Luigi Mariani, Pasquale Quattrone, Salvatore Alfieri, Paolo Bossi, Francesca Platini, Iolanda Capone, Lisa Licitra
Journal: Journal of Clinical Oncology (2021)

The activity of androgen-deprivation therapy (ADT) in androgen receptor-positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC.This was a single-institution phase II trial. A two-stage Simon's design was applied. The primary end point was confirmed objective response rate. Secondary end points were disease control rate, safety, progression-free survival, and overall survival. Patients were eligible when the following criteria were met: histologic diagnosis of AR-overexpressing SGC, measurable disease according to RECIST 1.1, clinical and/or radiologic progression on ADT, suppressed serum testosterone, and no limits for the number of previous chemotherapy lines. All patients received abiraterone 1 g daily plus prednisone 10 mg and luteinizing hormone-releasing hormone agonist until progression or unacceptable toxicities.From 2015 to 2019, 24 AR+ patients with SGC (23 men; median age 65.8 years) were treated within the study. The overall response rate was 21% (5 partial responses), with a disease control rate of 62.5%. The median duration of response was 5.82 months. Median progression-free survival was 3.65 months (95% CI, 1.94 to 5.89), and median overall survival was 22.47 months (95% CI, 6.74 to not reached). Objective response to previous ADT did not correlate with the activity of abiraterone. Adverse events (AEs) were recorded in 22 cases (92%) with grade 3 AEs in six patients (25%): fatigue (two), flushing (one), supraventricular tachycardia (one), and two non-drug-related AEs. No drug-related grade 4 or 5 AEs were recorded.Abiraterone plus luteinizing hormone-releasing hormone agonist is active and safe as a second-line option in AR-expressing, castration-resistant SGC.
Immunostimulatory Cancer-Associated Fibroblast Subpopulations Can Predict Immunotherapy Response in Head and Neck Cancer
Authors: Aleksandar Obradovic, Diana Graves, Michael Korrer, Yu Wang, Sohini Roy, Abdullah Naveed, Yaomin Xu, Adam Luginbuhl, Joseph Curry, Michael Gibson, Kamran Idrees, Paula Hurley, Peng Jiang, X. Shirley Liu, Ravindra Uppaluri, Charles G. Drake, Andrea Califano, Young J. Kim
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Cancer-associated fibroblasts (CAF) have been implicated as potential mediators of checkpoint immunotherapy response. However, the extensive heterogeneity of these cells has precluded rigorous understanding of their immunoregulatory role in the tumor microenvironment. Experimental Design: We performed high-dimensional single-cell RNA sequencing (scRNA-seq) on four patient tumors pretreatment and posttreatment from a neoadjuvant trial of patients with advanced-stage head and neck squamous cell carcinoma that were treated with the αPD-1 therapy, nivolumab. The head and neck CAF (HNCAF) protein activity profiles, derived from this cohort of paired scRNA-seq, were used to perform protein activity enrichment analysis on the 28-patient parental cohort of clinically annotated bulk transcriptomic profiles. Ex vivo coculture assays were used to test functional relevance of HNCAF subtypes. Results: Fourteen distinct cell types were identified with the fibroblast population showing significant changes in abundance following nivolumab treatment. Among the fibroblast subtypes, HNCAF-0/3 emerged as predictive of nivolumab response, while HNCAF-1 was associated with immunosuppression. Functionally, HNCAF-0/3 were found to reduce TGFβ-dependent PD-1+TIM-3+ exhaustion of CD8 T cells, increase CD103+NKG2A+ resident memory phenotypes, and enhance the overall cytolytic profile of T cells. Conclusions: Our findings demonstrate the functional importance of distinct HNCAF subsets in modulating the immunoregulatory milieu of human HNSCC. In addition, we have identified clinically actionable HNCAF subtypes that can be used as a biomarker of response and resistance in future clinical trials.
Cell Trafficking at the Intersection of the Tumor–Immune Compartments
Authors: Wenxuan Du, Praful Nair, Adrian Johnston, Pei-Hsun Wu, Denis Wirtz
Journal: Annual Review of Biomedical Engineering (2022)

Migration is an essential cellular process that regulates human organ development and homeostasis as well as disease initiation and progression. In cancer, immune and tumor cell migration is strongly associated with immune cell infiltration, immune escape, and tumor cell metastasis, which ultimately account for more than 90% of cancer deaths. The biophysics and molecular regulation of the migration of cancer and immune cells have been extensively studied separately. However, accumulating evidence indicates that, in the tumor microenvironment, the motilities of immune and cancer cells are highly interdependent via secreted factors such as cytokines and chemokines. Tumor and immune cells constantly express these soluble factors, which produce a tightly intertwined regulatory network for these cells’ respective migration. A mechanistic understanding of the reciprocal regulation of soluble factor–mediated cell migration can provide critical information for the development of new biomarkers of tumor progression and of tumor response to immuno-oncological treatments. We review the biophysical andbiomolecular basis for the migration of immune and tumor cells and their associated reciprocal regulatory network. We also describe ongoing attempts to translate this knowledge into the clinic.
Biomarkers for Adjuvant Endocrine and Chemotherapy in Early-Stage Breast Cancer: ASCO Guideline Update
Authors: Fabrice Andre, Nofisat Ismaila, Kimberly H. Allison, William E. Barlow, Deborah E. Collyar, Senthil Damodaran, N. Lynn Henry, Komal Jhaveri, Kevin Kalinsky, Nicole M. Kuderer, Anya Litvak, Erica L. Mayer, Lajos Pusztai, Rachel Raab, Antonio C. Wolff, Vered Stearns
Journal: Journal of Clinical Oncology (2022)

To update recommendations on appropriate use of breast cancer biomarker assay results to guide adjuvant endocrine and chemotherapy decisions in early-stage breast cancer.An updated literature search identified randomized clinical trials and prospective-retrospective studies published from January 2016 to October 2021. Outcomes of interest included overall survival and disease-free or recurrence-free survival. Expert Panel members used informal consensus to develop evidence-based recommendations.The search identified 24 studies informing the evidence base.Clinicians may use Oncotype DX, MammaPrint, Breast Cancer Index (BCI), and EndoPredict to guide adjuvant endocrine and chemotherapy in patients who are postmenopausal or age > 50 years with early-stage estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative (ER+ and HER2-) breast cancer that is node-negative or with 1-3 positive nodes. Prosigna and BCI may be used in postmenopausal patients with node-negative ER+ and HER2- breast cancer. In premenopausal patients, clinicians may use Oncotype in patients with node-negative ER+ and HER2- breast cancer. Current data suggest that premenopausal patients with 1-3 positive nodes benefit from chemotherapy regardless of genomic assay result. There are no data on use of genomic tests to guide adjuvant chemotherapy in patients with ≥ 4 positive nodes. Ki67 combined with other parameters or immunohistochemistry 4 score may be used in postmenopausal patients without access to genomic tests to guide adjuvant therapy decisions. BCI may be offered to patients with 0-3 positive nodes who received 5 years of endocrine therapy without evidence of recurrence to guide decisions about extended endocrine therapy. None of the assays are recommended for treatment guidance in individuals with HER2-positive or triple-negative breast cancer. Treatment decisions should also consider disease stage, comorbidities, and patient preferences.Additional information is available at www.asco.org/breast-cancer-guidelines.
CYFRA 21-1 Predicts Progression in Idiopathic Pulmonary Fibrosis: A Prospective Longitudinal Analysis of the PROFILE Cohort
Authors: Philip L. Molyneaux, William A. Fahy, Adam J. Byrne, Rebecca Braybrooke, Peter Saunders, Richard Toshner, Gesa Albers, Felix Chua, Elisabetta A. Renzoni, Athol U. Wells, Yakshitha Karkera, Eunice Oballa, Gauri Saini, Andrew G. Nicholson, R. Gisli Jenkins, Toby M. Maher
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive and inevitably fatal condition for which there are a lack of effective biomarkers to guide therapeutic decision making. Objectives: To determine the relationship between serum concentrations of the cytokeratin fragment CYFRA 21-1 and disease progression and mortality in individuals with IPF enrolled in the Prospective Observation of Fibrosis in the Lung Clinical Endpoints (PROFILE) study. Methods: CYFRA 21-1 was identified by immunohistochemistry in samples of human lung obtained at surgery. Concentrations of CYFRA 21-1 were measured using an ELISA-based assay in serum samples collected at baseline, 1 month, and 3 months from 491 individuals with an incident diagnosis of IPF who were enrolled in the PROFILE study and from 100 control subjects at baseline. Study subjects were followed for a minimum of 3 years after their first blood draw. Measurements and Main Results: CYFRA 21-1 localizes to hyperplastic epithelium in IPF lung tissue. Peripheral CYFRA 21-1 concentrations were significantly higher in subjects with IPF than in healthy control subjects in both the discovery (n = 132) (control: 0.96 ± 0.81 ng/ml; vs. IPF: 2.34 ± 2.15 ng/ml; P < 0.0001) and validation (n = 359) (control: 2.21 ± 1.54 ng/ml; and IPF: 4.13 ± 2.77 ng/ml; P < 0.0001) cohorts. Baseline concentrations of CYFRA 21-1 were able to distinguish individuals at risk of 12-month disease progression (C-statistic, 0.70; 95% confidence interval, 0.61–0.79; P < 0.0001) and were predictive of overall mortality (hazard ratio, 1.12 [95% confidence interval, 1.06–1.19] per 1 ng/ml increase in CYFRA 21-1; P = 0.0001). Furthermore, 3-month change in concentrations of CYFRA 21-1 separately predicted 12-month and overall survival in both the discovery and validation cohorts. Conclusions: CYFRA 21-1, a marker of epithelial damage and turnover, has the potential to be an important prognostic and therapeutic biomarker in individuals with IPF.
Abstract EP27: Development Of An Electronic Health Record-based Prediction Model For Hyperkalemia And Clinical Outcomes In Aldosterone Receptor Antagonist-prescribed Heart Failure Patients
Authors: Leanne Dumeny, Caitrin W McDonough, Julio Duarte, Larisa H Cavallari
Journal: Circulation (2022)

Background: Multiple clinical trials have evaluated the efficacy and safety of aldosterone receptor antagonist (ARA) use in heart failure (HF). They indicate that not all HF patients have the same level of hyperkalemia risk or morbidity risk reduction on ARAs. Identification of clinical predictors of patient response to ARAs would allow for treatment better tailored to the potential risks and benefits of each individual patient. The study’s objective was to identify a clinical predictive model for both hyperkalemia and all-cause mortality or HF-related hospitalization in ARA-prescribed patients with HF. Methods: This retrospective analysis used an anonymized EHR dataset of 8742 adult patients with a diagnosis of HF and an ARA prescription from the University of Florida health system. A list of potential clinical predictors identified from the literature was refined via feature selection using the least absolute shrinkage and selection operator (LASSO) technique. With the variables selected via LASSO, a logistic regression model for hyperkalemia and a Cox proportional hazards regression model for death or HF hospitalizations were used to identify the most significant predictors. Results: A model of 25 significant predictors for hyperkalemia in ARA-prescribed HF patients was identified (AUC = 0.70), including an ACE inhibitor/angiotensin receptor blocker (ARB) prescription, type 2 diabetes diagnosis, and chronic kidney disease diagnosis as predictors (Table 1). For death or HF hospitalizations, a predictive model of 20 significant predictors included a loop diuretic prescription, pulmonary hypertension diagnosis, and arrhythmia diagnosis (C-statistic = 0.76; Table 1). Conclusions: We developed an EHR-based model to predict hyperkalemia and morbidity and mortality in ARA-prescribed HF patients. Once validated, these findings should assist clinicians in providing more individualized and effective ARA therapy. Table 1: Significant Predictors in Model for Hyperkalemia and Death or HF Hospitalizations
Indications and Parameters Around Postoperative Radiation Therapy for Lung Cancer
Authors: Antonin Levy, Olaf Mercier, Cécile Le Péchoux
Journal: Journal of Clinical Oncology (2022)

Patients with locally advanced resected non-small-cell lung cancer present a high risk of relapse. Although adjuvant platinum-based chemotherapy has become the standard of care, the role of postoperative radiation therapy (PORT) has been controversial for years. In patients with incomplete resection, PORT should be proposed, on the basis of a strong consensus, despite the absence of randomized evidence. In patients with completely resected (R0) non-small-cell lung cancer, a meta-analysis showed poorer outcomes after PORT in the absence of mediastinal involvement (pN0 and pN1). In patients with pN2, the role of PORT was less clear and required further research. The meta-analysis included trials using older radiation techniques and poorer quality of surgery according to today's standards, and selection of patients was not positron emission tomography-based. Newer retrospective and nonrandomized studies and subgroup analyses of randomized trials evaluating adjuvant chemotherapy suggested a survival benefit of PORT in patients with pN2 R0. Two recent randomized trials (Lung ART and PORT-C) evaluating conformal PORT versus no PORT retrieved no disease-free survival advantage for stage IIIA-N2 patients, even if mediastinal relapse was significantly decreased with PORT. PORT had no effect on survival, possibly given the high rate of distant relapse and risk of additional cardiopulmonary toxicity. Ongoing and future analyses are planned in Lung ART to identify patients for whom PORT could be recommended. Incorporation of newer systemic treatments (immune checkpoint inhibitors or targeted therapy in oncogene-addicted patients) is underway in the neoadjuvant and/or adjuvant setting. Better identification of patients at a high risk of disease recurrence, with analysis of circulating tumor DNA, on the basis of the detection of postsurgical minimal (or molecular) residual disease is warranted in future studies.
<scp>Treatment‐free</scp> remission in patients with chronic myeloid leukemia following the discontinuation of tyrosine kinase inhibitors
Authors: Fadi G. Haddad, Koji Sasaki, Ghayas C. Issa, Guillermo Garcia‐Manero, Farhad Ravandi, Tapan Kadia, Jorge Cortes, Marina Konopleva, Naveen Pemmaraju, Yesid Alvarado, Musa Yilmaz, Gautam Borthakur, Courtney DiNardo, Nitin Jain, Naval Daver, Nicholas J. Short, Elias Jabbour, Hagop Kantarjian
Journal: American Journal of Hematology (2022)

Tyrosine kinase inhibitors (TKIs) discontinuation in patients with Philadelphia-chromosome-positive chronic myeloid leukemia (Ph-positive CML) is increasingly considered. We aim to evaluate the outcome of patients with CML who discontinued TKIs, and determine the factors associated with differences in the success rates of treatment-free remission (TFR). Patients with Ph-positive CML treated between October 1999 and February 2017 who discontinued therapy were analyzed. A major molecular response (MMR) was defined as BCR-ABL1/ABL1 ratio on the International Scale ≤0.1%. TFR failure was defined as the loss of MMR on any single test. We analyzed TFR rates according to duration and depth of response, and conducted a multivariate analysis for factors associated with loss of MMR. Two-hundred and eighty-four patients were analyzed; 199 patients (70%) electively discontinued TKIs. At a median follow-up of 36 months (95% confidence interval, 32-40) after TKI discontinuation, 53 patients (19%) lost MMR. The estimated 5-year TFR rate was 79%. All but one patient regained MMR after resuming therapy. The estimated 5-year TFR rates were higher with MR4 and MR4.5 ≥5 years, compared with MR4 <5 years (87% vs. 92% vs. 64%; p < .0001). By multivariate analysis, only the duration of MR4 or MR4.5 ≥5 years before stopping treatment was associated with a lower risk of loss of MMR. In summary, TFR is safe and feasible in patients with Ph-positive CML on TKI therapy. Achieving MR4 or MR4.5 for at least 5 years is correlated with a better outcome.
Long Noncoding RNA-Maternally Expressed Gene 3 Contributes to Hypoxic Pulmonary Hypertension
Authors: Yan Xing, Xiaodong Zheng, Yao Fu, Jing Qi, Minghui Li, Mingfei Ma, Shuang Wang, Shuzhen Li, Daling Zhu
Journal: Molecular Therapy (2021)

(Molecular Therapy 27, 2166–2181; December 2019) In the originally published version of this article, there was overlap between several control images in Figure 2A. We have replaced these images with a new set of control images from each group to show the specificity of the probes. This correction does not alter the conclusions of the original article. The authors regret this error. Long Noncoding RNA-Maternally Expressed Gene 3 Contributes to Hypoxic Pulmonary HypertensionXing et al.Molecular TherapyAugust 22, 2019In BriefIncreasing evidence indicates that lncRNAs are implicated in pulmonary hypertension. Xing et al. demonstrate that lncRNA-MEG3 contributes to PASMCs proliferation and cell-cycle progression through interacting with and facilitating miR-328-3p degradation. Lung-specific lncRNA-MEG3 knockdown rescues hypoxia-induced pulmonary hypertension, which is prevented by anti-miR-328-3p therapy. Full-Text PDF Open Archive
FDG PET/CT in Metastatic Spindle Cell Sarcoma of Penile Origin
Authors: Shubham Anil Kale, Archi Agrawal, Santosh Menon, Amit Joshi, Vedang Murthy, Ganesh Bakshi, Gagan Prakash, Nilendu Purandare, Sneha Shah, Ameya Puranik, Venkatesh Rangarajan
Journal: Clinical Nuclear Medicine (2022)

Spindle cell sarcoma is a connective tissue tumor usually involving bone or muscle. Penis is an unusual and very rare site for the primary involvement of the tumor, especially mesenchymal tumor. We here present a case of a 27-year-old man diagnosed with spindle cell sarcoma of penile origin in which FDG PET/CT was done as part of workup.