tbuckley/cabot-search huggingface dataset:
Association of ECOG performance status with efficacy in patients receiving panitumumab with best supportive care (BSC) vs BSC alone for chemorefractory metastatic colorectal cancer.
Authors: Eduard Vrdoljak, Anneli Elme, Zvonko Kusic, Joon Oh Park, Anghel Adrian Udrea, Sun Young Kim, Joong Bae Ahn, Ricardo Villalobos, Krishnan Srinivasan, Ante Bilic, Nebojsa Manojlovic, Jun Dong, Xuesong Guan, Catherine Lofton-Day, A. Scott Jung, Tae Won Kim
Journal: Journal of Clinical Oncology (2016)

e15018 Background: Historically, performance status (PS) has been used as a factor to predict treatment tolerability to cytotoxic chemotherapy. Panitumumab (pmab), a fully human monoclonal antibody directed against human epidermal growth factor receptor, is used to treat wild type (WT) RAS metastatic colorectal cancer (mCRC) in combination with cytotoxic chemotherapy or as monotherapy. Methods: Patients (pts) in study 20100007 (NCT01412957) were randomized (stratified by Eastern Cooperative Oncology Group [ECOG] PS ≤ 1 vs 2 and region) 1:1 to receive either pmab (6 mg/kg every 14 days, IV) + BSC or BSC alone. Here, we present a pre-specified descriptive analysis of efficacy by PS in WT RASpts based on the primary analysis. Results: 270 WT RAS mCRC pts were included for this analysis. Efficacy analyses of overall survival (OS) and progression-free survival (PFS) by PS are shown (Table). The results favored the pmab + BSC arm in both PS ≤ 1 and PS = 2 groups (hazard ratio [HR] 0.721 and 0.335 for OS; and HR 0.463 and 0.339 for PFS) with nominal P-values all less than 0.05. Although pts with PS = 2 had a trend for more adverse events (AEs) ≥ 3 compared to pts with PS ≤ 1, the percentage of AEs ≥ 3 were comparable in each arm for PS = 2 (66.7% in pmab + BSC; 54.5% in BSC). Treatment discontinuation rates were relatively low in both PS ≤ 1 (7.1%) and PS = 2 (13.3%) groups. Conclusions: Addition of pmab provided survival advantage not only in pts with PS ≤ 1 but appears to do so in pts with PS = 2 despite the expected challenges associated with diminished PS. The results suggest that pmab may be a viable treatment for pts whose options are further constrained due to decline in PS. Clinical trial information: NCT01412957. Baseline PS 0 or 1 Baseline PS 2 Pmab + BSC (N = 127) BSC (N = 117) Pmab + BSC (N = 15) BSC (N = 11) OS Median (95% CI) - (months) 10.5 (9.1 – 12.8) 7.4 (5.6 – 10.3) 7.9 (4.3 – 9.7) 3.4 (1.0 – 3.8) Hazard ratio (95% CI) 0.721 (0.536, 0.970) 0.335 (0.138, 0.812) Log-rank P-value 0.0295 0.0116 PFS Median (95% CI) - (months) 5.3 (3.6 – 5.4) 1.8 (1.6 – 2.3) 3.4 (1.7 – 7.1) 1.1 (0.9 – 1.6) Hazard ratio (95% CI) 0.463 (0.353, 0.607) 0.339 (0.137, 0.839) Log-rank P-value < 0.0001 0.0152
No recovery of replication-competent HIV-1 from human liver macrophages
Authors: Abraham J. Kandathil, Sho Sugawara, Ashish Goyal, Christine M. Durand, Jeffrey Quinn, Jaiprasath Sachithanandham, Andrew M. Cameron, Justin R. Bailey, Alan S. Perelson, Ashwin Balagopal
Journal: Journal of Clinical Investigation (2018)

Long-lived HIV-1 reservoirs that persist despite antiretroviral therapy (ART) are a major impediment to a cure for HIV-1. We examined whether human liver macrophages (LMs), the largest tissue macrophage population, comprise an HIV-1 reservoir. We purified LMs from liver explants and included treatment with a T cell immunotoxin to reduce T cells to 1% or less. LMs were purified from 9 HIV-1-infected persons, 8 of whom were on ART (range 8-140 months). Purified LMs were stimulated ex vivo and supernatants from 6 of 8 LMs from persons on ART transmitted infection. However, HIV-1 propagation from LMs was not sustained except in LMs from 1 person taking ART for less than 1 year. Bulk liver sequences matched LM-derived HIV-1 in 5 individuals. Additional in vitro experiments undertaken to quantify the decay of HIV-1-infected LMs from 3 healthy controls showed evidence of infection and viral release for prolonged durations (>170 days). Released HIV-1 propagated robustly in target cells, demonstrating that viral outgrowth was observable using our methods. The t1/2 of HIV-1-infected LMs ranged from 3.8-55 days. These findings suggest that while HIV-1 persists in LMs during ART, it does so in forms that are inert, suggesting that they are defective or restricted with regard to propagation.
Osteosarcoma prognostic nomograms for predicting the 10-year probability of mortality and recurrence.
Authors: Haotong Wang, Ruoyu Miao, Alex Jacobson, Saveli Goldberg, David C. Harmon, Gregory Cote, Francis J Hornicek, Kevin Raskin, Gunnlaugur Nielsen, Thomas F. DeLaney, Edward Choy, Yen-Lin Chen
Journal: Journal of Clinical Oncology (2017)

11020 Background: The multidisciplinary approach in treatment of osteosarcoma has been well established and well adopted nationwide. This study combined the clinical prognostic factors at initial presentation into a nomogram to predict local control (LC), metastasis free survival (MFS), and overall survival (OS) for patients with non-metastatic bone osteosarcoma. Methods: We reviewed 397 osteosarcoma patients treated from 1995 to 2014. Patients with metastatic disease at diagnosis or limited follow up were excluded, resulting in 283 cases for analysis. Clinical and pathologic variables were recorded. Predictive variables included age at diagnosis, gender, previous radiation history, site, tumor size, histologic subtype, histologic grade, extra-osseous extension (EOE), lymphovascular invasion (LVI), necrosis rate and margin. The multivariate Cox proportional hazards regression was used to analyze survival outcomes and risk variables. Results: At 10 years, LC was 70.4% (95% confidence interval, CI: 64.0%-76.7%), MFS was 64.7% (95% CI: 58.1%-71.3%), and OS was 61.5% (95% CI: 54.9%-68.1%). Multivariate Cox model identified age (p = 0.033), site (p = 0.020), EOE (p = 0.017), LVI (p = 0.011), and margin (p = 0.039) were correlated with LC; age (p = 0.028), tumor size (p &lt; 0.001), histologic grade (p = 0.039), and LVI (p = 0.014) were correlated with MFS; whereas age (p &lt; 0.001), prior radiation history (p = 0.010), tumor size (p = 0.002), histologic subtype (p = 0.012), EOE (p = 0.002), and LVI (p = 0.001) were associated with OS. The nomograms were drawn on the basis of the Cox regression model and were internally validated using bootstrapping, with predictive accuracy of ±7.2% for 10-year LC, ±7.4% for 10-year MFS, and ±7.5% for 10-year OS. Conclusions: Nomograms have been developed to predict the 10-year local-control failure, recurrence and death. We suggest that this tool at presentation may be useful for individualized risk evaluation, patient counseling, and making clinical decisions.
Evaluation of cervical cancer control plans with human papilloma virus detection in Tucumán, Argentina: December 2014-January 2016.
Authors: Silvia Victoria Holgado, Conrado Oscar Cinto, Simon Perez, Fernanda Arrieta, Adriana Gonzalez, Paola Lorenzetti, Fernanda Suedan, Marina Jimenez, Juan Jose Zarba
Journal: Journal of Clinical Oncology (2016)

e23124 Background: HPV testing is considered an important strategy in the cervical cancer prevention. Since April, 2014 the FDA approved the use of one HPV DNA test (T-HPV). Concurrent HPV testing and cervical cytology (co-testing) is an approved and promising alternative to cytology alone in women aged 30 and older. T-HPV is highly sensitive (95%) and has a good negative predictive value allowing spacing interval screening. Tucuman is the second province in Argentina where this screening method is applied. Methods: 17,677 samples from non-pregnant, aged 30 and older women without health insurance were included. 2 collection methods were applied:
Three Multicenter, Randomized, Double‐Blind, Placebo‐Controlled Studies Evaluating the Efficacy and Safety of Ustekinumab in Axial Spondyloarthritis
Authors: Atul Deodhar, Lianne S. Gensler, Joachim Sieper, Michael Clark, Cesar Calderon, Yuhua Wang, Yiying Zhou, Jocelyn H. Leu, Kim Campbell, Kristen Sweet, Diane D. Harrison, Elizabeth C. Hsia, Désirée van der Heijde
Journal: Arthritis & Rheumatology (2018)

Objective To evaluate the efficacy and safety of ustekinumab in 3 randomized, placebo‐controlled studies in patients with axial spondyloarthritis (SpA). Studies 1 and 2 included patients with radiographic axial SpA (anti–tumor necrosis factor [anti‐ TNF ]–naive patients and patients with inadequate response or intolerance to anti‐ TNF , respectively); study 3 patients had nonradiographic axial SpA. Methods In all 3 studies, patients were randomly assigned (1:1:1) to receive subcutaneous ustekinumab at 45 mg or 90 mg or placebo up to 24 weeks, after which placebo‐treated patients were rerandomized to receive ustekinumab at 45 mg or 90 mg. The primary end point in studies 1 and 2 was the proportion of patients who met the Assessment of SpondyloArthritis international Society criteria for 40% improvement in disease activity (achieved an ASAS 40 response). The primary end point in study 3 was the proportion of patients who achieved an ASAS 20 response. Other disease activity and safety measures were also evaluated. A week 24 analysis of study 1 was preplanned to determine continuation of studies 2 and 3. Results For study 1, the primary and major secondary end points were not met, and the study was discontinued. As a result, studies 2 and 3 were prematurely discontinued before they were fully enrolled. For all 3 studies, neither ustekinumab dose group demonstrated clinically meaningful improvement over placebo on key efficacy end points. The proportion of patients experiencing adverse events in the ustekinumab groups was consistent with that in previous studies. Conclusion In these 3 placebo‐controlled trials, efficacy of ustekinumab in the treatment of axial SpA was not demonstrated. The safety profile was consistent with that of studies in other indications.
A phase I/II study to assess the safety and efficacy of pazopanib (PAZ) and pembrolizumab (PEM) in patients (pts) with advanced renal cell carcinoma (aRCC).
Authors: Simon Chowdhury, David F. McDermott, Martin Henner Voss, Robert E. Hawkins, Paola Aimone, Maurizio Voi, Naëije Isabelle, Yi Wu, Jeffrey R. Infante
Journal: Journal of Clinical Oncology (2017)

4506 Background: PAZ is indicated for the treatment of aRCC. The combination of an anti-angiogenic agent and immunotherapy may improve anti-tumor activity. We report preliminary safety and efficacy results of the phase I part of the study. Methods: Twenty pts were originally enrolled in cohorts A and B assessing PAZ 800 mg and 600 mg, respectively, both with 2mg/kg (Q2W and then Q3W) PEM to determine the maximum tolerated dose. Due to dose limiting liver toxicity, cohort C was opened to assess if the sequential schedule of 9 weeks PAZ run-in followed by PAZ+PEM would improve safety. Strict safety criteria for initiating PAZ+PEM were set. The data from this ongoing study are presented given the limited information available on the combination of TKI + PD-1 inhibitors in RCC. Results: Overall, 35 pts were treated; 5 out of 15 pts in cohort C received PAZ+PEM at the data cut-off. Three dose-limiting toxicities (DLT) occurred in cohort C in pts receiving PAZ+PEM; updated DLTs in all cohorts are reported in Table. G3/4 AEs were observed in 90% of pts in cohorts A and B and in 80% of pts in cohort C receiving PAZ+PEM. No G3/4 ALT/AST elevation was reported in cohort C PAZ+PEM while they were observed in 70% and 60% in cohorts A and B, respectively. Best overall response (CR+PR) was reported in 6, 2 and 1 pts receiving PAZ+PEM in cohorts A, B and C, respectively. Conclusions: Results from cohorts A and B showed significant hepatotoxicity. The sequential schedule PAZ → PAZ+PEM has shown reduced hepatotoxicity and preliminary signs of efficacy but overall limited tolerability. PAZ+PEM is not suitable to test in a larger cohort. Clinical trial information: 2013-003785-14. [Table: see text]
A nomogram to predict overall survival in colorectal cancer patients based on new inflammation-nutrition score and TNM stage.
Authors: Shiki Fujino, Norikatsu Miyoshi, Masaru Sasaki, Satoshi Ishikawa, Kazuhiro Saso, Yusuke Takahashi, Masayoshi Yasui, Masayuki Ohue, Taishi Hata, Chu Matsuda, Tsunekazu Mizushima, Yuichiro Doki, Masaki Mori
Journal: Journal of Clinical Oncology (2018)

e15625 Background: Inflammation, nutrition and immunity of patients are known to relate the prognosis of malignant tumors. Several prognostic scores were reported, such as modified Glasgow Prognostic Score (mGPS), and the prognostic nutritional index (PNI). We developed new Osaka Prognostic Score (OPS) and it was independent significant factor in overall survival (OS). Herein, we reported a novel nomogram for predicting cancer prognosis based on patient’s factors (OPS) and cancer stage. Methods: 569 CRC patients were retrospectively investigated from 2007 to 2013. 431 patients who underwent surgical resection of primary tumor at the Osaka International Cancer Institute from 2007 to 2012 were included in training-set (TS). 138 patients who underwent surgical resection at Osaka University from 2011 to 2012 were included in validation-set (VS). OPS was scored by CRP ( > 1.0 mg/dL), albumin ( < 3.5 g/dL), and lymphocyte ( < 1500 counts). Each factor was calculated as 1 point, and added. Patients were classified into OPS 1 (0-1 point), OPS 2 (2 points), and OPS 3 (3 points). The nomogram to predict overall survival was constructed by OPS and cancer stage. It was developed by TS and validated by VS. Results: In TS, 372 patients were OPS 1, 46 patients were OPS 2, and 13 patients were OPS 3. 82 patients were stage I, 135 patients were stage II, 167 patients were stage III, and 47 patients were stage IV according to UICC classification. The concordance-index (C-index) of TNM stage to predict OS was 0.751 and the C-index of OPS classification was 0.684. The nomogram to predict overall survival was developed by TNM stage and OPS classification and the C-index was 0.818 in TS. It was validated by VS and the C-index was 0.729. Conclusions: We developed a novel and reliable prognostic score, OPS and nomogram. Integrating TNM stage and OPS may predict prognosis with high accuracy in each patient.
Rapid CLIP dissociation from MHC II promotes an unusual antigen presentation pathway in autoimmunity
Authors: Yoshinaga Ito, Orr Ashenberg, Jason Pyrdol, Adrienne M. Luoma, Orit Rozenblatt-Rosen, Matan Hofree, Elena Christian, Lucas Ferrari de Andrade, Rong En Tay, Luc Teyton, Aviv Regev, Stephanie K. Dougan, Kai W. Wucherpfennig
Journal: The Journal of Experimental Medicine (2018)

A number of autoimmunity-associated MHC class II proteins interact only weakly with the invariant chain-derived class II-associated invariant chain peptide (CLIP). CLIP dissociates rapidly from I-Ag7 even in the absence of DM, and this property is related to the type 1 diabetes-associated β57 polymorphism. We generated knock-in non-obese diabetic (NOD) mice with a single amino acid change in the CLIP segment of the invariant chain in order to moderately slow CLIP dissociation from I-Ag7 These knock-in mice had a significantly reduced incidence of spontaneous type 1 diabetes and diminished islet infiltration by CD4 T cells, in particular T cells specific for fusion peptides generated by covalent linkage of proteolytic fragments within β cell secretory granules. Rapid CLIP dissociation enhanced the presentation of such extracellular peptides, thus bypassing the conventional MHC class II antigen-processing pathway. Autoimmunity-associated MHC class II polymorphisms therefore not only modify binding of self-peptides, but also alter the biochemistry of peptide acquisition.
Gender effect on phenotype and genotype in patients with post-polycythemia vera and post-essential thrombocythemia myelofibrosis: results from the MYSEC project
Authors: Daniela Barraco, Barbara Mora, Paola Guglielmelli, Elisa Rumi, Margherita Maffioli, Alessandro Rambaldi, Marianna Caramella, Rami Komrokji, Jason Gotlib, Jean Jacques Kiladjian, Francisco Cervantes, Timothy Devos, Francesca Palandri, Valerio De Stefano, Marco Ruggeri, Richard T. Silver, Giulia Benevolo, Francesco Albano, Michele Merli, Daniela Pietra, Tiziano Barbui, Giada Rotunno, Mario Cazzola, Toni Giorgino, Alessandro Maria Vannucchi, Francesco Passamonti
Journal: Blood Cancer Journal (2018)
TCT-745 Early results of Revivent Procedure in the Treatment of Patients with Left Ventricular Dilatation and Heart Failure due to Ischemic Cardiomyopathy
Authors: Yan Wang, Guosheng Xiao, None Bin Wang, Zhi Lin, Keke Lai, Maolong Su, Hongmei Wen, Jian Wang, Guoming Zhang, Cuilian Dai, Lon Annest
Journal: Journal of the American College of Cardiology (2018)
Prescription trends of everolimus in non-elderly cancer patients with private insurance in the United States.
Authors: Yan Xing, Ying Xu, Funda Meric-Bernstam, Jenny Chee Ning Chang, Ya-Chen T. Shih
Journal: Journal of Clinical Oncology (2017)

e18016 Background: The use of targeted oral cancer medications has increased significantly since 2001. Everolimus, an mTOR inhibitor was first approved for cancer treatment by FDA as second line for patients with advanced renal cancer. Subsequently it has been approved for advanced pancreatic neuroendocrine tumor (NET) in 2011 and breast cancer in 2012 respectively. Off-label use is common in oncology practice. The objective of this study is to assess prescription trends, especially off-label use of everolimus, among non-elderly cancer patients with private insurance in the United States from 2009 to 2014. Methods: Data from the MarketScan database were analyzed. Between 2009 to 2014, 4,728 cancer patients with at least one everolimus prescription were included in the analyses. The diagnosis which incurred the most recently to the initial everolimus use in each calendar year was recorded. Off-label use was defined as using everolimus by all of the cancer types except of renal cancer in 2009-2014, NET in 2011-2014 and breast cancer in 2012-2014. Results: The number of patients received everolimus has increased significantly from 243 in 2009 to 1,194 in 2014. The most common diagnoses associated with everolimus use were breast cancer (42%), followed by renal cancer (24%), and NET (7%). Off-label use of everolimus increased from 29% in 2009 to 47% in 2011 then decreased to 23% in 2014. The 3 most common diagnoses associated with off-label use of everolimus were secondary malignancies (30.7%), breast cancer (10.4%) and liver cancer (5%) in 2009-2011, compared to secondary malignancies (47.3%), brain cancer (4.2%) and lung cancer (3.9%) in 2012-2014. The off-label use in female has decreased significantly from 32% in 2009 to 19% in 2014 (p = 0.03). There was no statistical difference in off-label use of everolimus by geographic region. Conclusions: Analyses of MarketScan data suggest off-label use of everolimus is common among US cancer patients, especially in lung, liver and brain cancer and secondary malignancies after the approved indication was expanded to breast cancer in 2012. Further research of the factors associated with off-label use of everolimus and its economic implication is needed.
The impact of chemotherapy on the immunophenotype of peripheral blood lymphocytes and survival in patients with non-small cell lung cancer.
Authors: Mohanad Aldarouish, Yan Chen, Shiya Zheng, Anwei Dai, Cailian Wang
Journal: Journal of Clinical Oncology (2018)

e24125 Background: Recently, there has been a growing interest in lung cancer immunotherapy due to its preliminary results in achieving meaningful treatments responses. We conducted this research for more understanding the immunophenotyping profile of peripheral blood from patients with advanced non-small cell lung cancer (NSCLC) after chemotherapy and the correlation with patients’ survival. Methods: Peripheral blood samples were collected from 15 healthy donors and 35 patients with advanced NSCLC after two cycles of chemotherapy. Phenotypic analysis of lymphocyte subsets (absolute numbers and frequencies) was performed one week after two cycles chemotherapy. The correlation between post-chemotherapy levels of lymphocyte subsets and patients’ progression free survival (PFS) was estimated by a Kaplan–Meier method. Results: After chemotherapy, there was no significant difference in the frequency of CD8+ T lymphocytes, PD-1+CD8+, Th2 and Th17 cells between patients and healthy subjects. The frequencies of PD-1+CD4+ and Treg cells were elevated in patients’ peripheral blood compared to healthy donors, in contrast to the frequencies of NK and Th1 cells. PFS was significantly better in patients with low percentage of PD-1+CD4+T cells than those with high percentage (8.1 months vs. 5.2 months, P = 0.02). Pateints with high content of Th1 cells showed higher PFS than those with low content (9.1 months vs. 5.6 months, P = 0.04). Even though the difference did not reach statistical significance, the low percentages of Th17 and Treg cells were correlated with longer PFS (9.2 months vs. 6.3, P = 0.15 and 9.1 months vs. 6.1 months, P = 0.17; respectively). There was no significant correlation between patients’ PFS and the levels of CD8+ T lymphocytes, PD-1+CD8+, NK and Th2 cells. Conclusions: The expression of PD-1 on CD4+ T cells has a crucial role in the progression of NSCLC and could be used as a prognostic factor. The high level of Th1 cells could predict better clinical outcomes of chemotherapy. Further studies are needed to elucidate the exact function of Th17 cells due to their bi-dual role. CD8+ T, NK, Th2 cells in patients’ peripheral blood have no direct correlation with clinical outcomes.