tbuckley/cabot-search huggingface dataset:
Prognostic factors of overall (OS) and relapse-free survival (RFS) for patients with acute myeloid leukemia (AML) in remission after intensive chemotherapy (IC): Multivariate analyses from the QUAZAR AML-001 trial of oral azacitidine (Oral-AZA).
Authors: Gail J. Roboz, Andrew H. Wei, Farhad Ravandi, Christopher Pocock, Pau Montesinos, Hervé Dombret, Kimmo Porkka, Ignazia La Torre, Barry Skikne, Jianhua Zhong, C. L. Beach, Hartmut Dohner
Journal: Journal of Clinical Oncology (2021)

7014 Background: Demographic and disease factors influence outcomes for patients (pts) with AML. In the phase 3 QUAZAR AML-001 trial, Oral-AZA significantly prolonged OS and RFS vs. placebo (PBO) for pts with AML in first remission after IC (Wei, NEJM, 2020). Univariate analyses showed OS and RFS benefits with Oral-AZA vs. PBO across pt subgroups defined by baseline (BL) characteristics. MV analyses were performed to identify BL characteristics independently predictive of OS/RFS in QUAZAR AML-001, and to assess Tx effects of Oral-AZA vs. PBO on survival when adjusted for BL factors. Methods: Pts were aged ≥55 yrs with AML in complete remission (CR) or CR with incomplete count recovery (CRi) after induction ± consolidation. Within 4 months of CR/CRi, pts were randomized 1:1 to receive Oral-AZA 300 mg or PBO for 14d/28d cycle. Cox proportional hazards models were used to estimate Tx effects of Oral-AZA vs. PBO on OS and RFS, adjusting for BL age, sex, ECOG PS score, cytogenetic risk at diagnosis (Dx), prior MDS, geographic region, CR/CRi after induction (per investigator) and at BL (per sponsor), MRD status, receipt of consolidation, number of consolidation cycles, platelet count, and ANC. In a stepwise procedure, randomized Tx and BL variables were selected incrementally into a Cox model if P ≤ 0.25. After each addition, the contribution of the covariate adjusted for other covariates in the model was evaluated and retained in the model if P ≤ 0.15. Results : Oral-AZA Tx remained a significant independent predictor of improved OS (HR 0.70) and RFS (HR 0.57) vs. PBO after controlling for BL characteristics (Table). MRD status, cytogenetic risk, and pt age were each also independently predictive of OS and RFS. Response after induction (CR vs. CRi) and BL ANC were predictive of OS but not RFS, whereas prior MDS, CR/CRi at BL, and number of consolidation cycles were only predictive of RFS. Conclusions: Tx with Oral-AZA reduced the risk of death by 30% and risk of relapse by 43% vs. PBO independent of BL characteristics. Cytogenetic risk at Dx, MRD status, and pt age also independently predicted survival outcomes. Clinical trial information: NCT01757535. [Table: see text]
Impact of cancer on the risk of unplanned 30-day readmissions.
Authors: Alexander Qian, Edmund Qiao, Vinit Nalawade, Nikhil V. Kotha, Rohith S. Voora, James Don Murphy
Journal: Journal of Clinical Oncology (2021)

6581 Background: Hospital readmission are associated with unfavorable patient outcomes and increased costs to the healthcare system. Devising interventions to reduce risks of readmission requires understanding patients at highest risk. Cancer patients represent a unique population with distinct risk factors. The purpose of this study was to define the impact of a cancer diagnosis on the risks of unplanned 30-day readmissions. Methods: We identified non-procedural hospital admissions between January through November 2017 from the National Readmission Database (NRD). We included patients with and without a cancer diagnosis who were admitted for non-procedural causes. We evaluated the impact of cancer on the risk of 30-day unplanned readmissions using multivariable mixed-effects logistic regression models. Results: Out of 18,996,625 weighted admissions, 1,685,099 (8.9%) had record of a cancer diagnosis. A cancer diagnosis was associated with an increased risk of readmission compared to non-cancer patients (23.5% vs. 13.6%, p &lt; 0.001). However, among readmissions, cancer patients were less likely to have a preventable readmission (6.5% vs. 12.1%, p &lt; 0.001). When considering the 10 most common causes of initial hospitalization, cancer was associated with an increased risk of readmission for each of these 10 causes (OR range 1.1-2.7, all p &lt; 0.05) compared to non-cancer patients admitted for the same causes. Compared to patients aged 45-64, a younger age was associated with increased risk for cancer patients (OR 1.29, 95%CI [1.24-1.34]) but decreased risk for non-cancer patients (OR 0.65, 95%CI [0.64-0.66]). Among cancer patients, cancer site was the most robust individual predictor for readmission with liver (OR 1.47, 95%CI [1.39-1.55]), pancreas (OR 1.36, 95%CI [1.29-1.44]), and non-Hodgkin’s lymphoma (OR 1.35, 95%CI [1.29-1.42]) having the highest risk compared to the reference group of prostate cancer patients. Conclusions: Cancer patients have a higher risk of 30-day readmission, with increased risks among younger cancer patients, and with individual risks varying by cancer type. Future risk stratification approaches should consider cancer patients as an independent group with unique risks of readmission.
Deep learning survival model on transcriptomes level in patients with non-small cell lung cancer.
Authors: Hao Yu, Li Yang, Ka-On Lam, Jian-Yue Jin, Chen Hu, Feng-Ming Spring Kong
Journal: Journal of Clinical Oncology (2021)

e20518 Background: Non-small cell lung cancer (NSCLC) is associated with poor prognosis. Global gene expression profiling with overall survival (OS) may help improving individualize survival. In this study, we identify biological important gene clusters and studied their prognostic abilities for OS by deep learning method. Methods: Using GEO genomics data repository, we identified 196 NSCLC patients (trainset: GSE37745) and 181 NSCLC patients (testset: GSE50081) with clinical information and long-term follow-up. In both cohorts, expression profiling was performed on RNA from tumor tissues using Affymetrix microarrays HG-U133-Plus2; and normalized using the Robust Multiarray Averaging (RMA). We established deep learning survival models through neural network extension of the Cox regression model for predicting OS, which were developed by 5-folds cross-validation in GSE37745 and independently validated in GSE50081. Significant RNA-seq and clinical variables were multiple inputs. Concordance index (CI) was evaluated and compared with multivariable Cox regression. Then we conducted Uniform Manifold Approximation and Projection (UMAP) using weights in hidden layer of the model for clustering the important RNA-seq and then performed enrichment analysis though GO/KEGG for revealing biological progresses. Results: Total 1039 RNA-seq levels were found significant with OS ( P &lt; 0.05) by Cox proportional hazard model adjusted by clinical variables (age, gender, cancer stage, histology) in trainset. The deep learning survival model with 20 most significant RNA-seq and clinical variables had best average performances as CI = 0.74±0.04 in trainset (GSE37745) and CI = 0.68±0.06 in testset (GSE50081) in 10 iterations, better than multivariable Cox regression ( P &lt; 0.05). The deep learning survival model with all significant RNA-seq were also established and the weights in the hidden layer were clustered by UMAP into 5 positive and 5 negative clusters. The clusters were enriched, such as in positive clusters, negative regulation of RNA metabolic process, negative regulation of RNA biosynthetic process and positive regulation of protein modification process were top three significant biological processes for shorten survival; while in negative clusters, DNA metabolic process, positive regulation of phosphate metabolic process and positive regulation of RNA metabolic process were the top three for prolonged survival. Conclusions: In this study, the deep learning survival algorithm was established for survival prediction based on a transcriptome level in patients with NSCLC. Given the models’ robustness and better performances, our study would be useful at predicting and applying more biological information for survival.
Loss of hepatocyte identity following aberrant YAP activation: A key mechanism in alcoholic hepatitis
Authors: Mohamed Bou Saleh, Alexandre Louvet, Line Carolle Ntandja-Wandji, Emmanuel Boleslawski, Viviane Gnemmi, Guillaume Lassailly, Stéphanie Truant, François Maggiotto, Massih Ningarhari, Florent Artru, Emilie Anglo, Pau Sancho-Bru, Anne Corlu, Josepmaria Argemi, Julie Dubois-Chevalier, Sébastien Dharancy, Jérôme Eeckhoute, Ramon Bataller, Philippe Mathurin, Laurent Dubuquoy
Journal: Journal of Hepatology (2021)
Abstract 14923: Consumption of Mixed Nuts Increases Satiety Without Altering Postprandial Blood Glucose and Insulin in Healthy Adults
Authors: Kathryn Ward, Andrew Ordille, Christine Kent, Mee Young Hong
Journal: Circulation (2017)

Introduction: Despite the rise in the diagnosis of both diabetes and cardiovascular disease in the United States each year, the majority of these diagnoses are preventable with proper nutrition and...
Abstract 17217: Brown Adipocyte Adipokine Il18 Mediates Thermogenesis and Insulin Sensitivity Through Their Divergent Effects of Its Two Receptors
Authors: Xian Zhang, Songyuan Luo, Wang Minjie, Zhiyong Deng, Guo-Ping Shi
Journal: Circulation (2019)

Introduction: Interleukin 18 (IL18) concentration is elevated in the circulation after the development of obesity and type-2 diabetes. Recent studies suggest that deficiency of IL18 leads to hyperp...
A novel DNA methylation marker for the urine-based liquid biopsies to detect bladder cancer.
Authors: Tao Zeng, Huanhuan Deng, Rongsong Zhao, Longwu Huang, Yun Gong, Yuetian Zhu, Qingping Wang, Feng Li, Lirong Liu, Yan Qi, Xianshu Wang, Hongzhi Zou
Journal: Journal of Clinical Oncology (2021)

e16503 Background: For bladder cancer (BC), the 5-year survival rate for patients with localized tumors can reach as high as 92%, but only 45% for those with tumors spreading to nearby regions. Cystoscopy combined with tissue biopsy can miss 10-40% of the cancer cases due to multiple factors. Meanwhile, the method is invasive, causing physical discomfort and psychological trauma for the patients. Therefore, development of a noninvasive, sensitive, and specific diagnostic alternative is needed. By analyzing TCGA data and improving analytic technology currently available, we have developed an easy-to-use, convenient, and accurate detection approach for BC relying on a single methylation marker. Methods: We searched TCGA database and selected a total of 366 candidate markers including those that have been published for subsequent examination and analyzed 446 primer pairs and probe sets. Using quantitative methylight method, we narrowed the field down to top 5 performers for subsequent urine-based testing of 270 samples. Finally, two markers were selected for validation testing in a group of 530 urine samples, consisting of 161 bladder cancers, 244 normal controls, 80 renal carcinomas, and 45 carcinomas of renal pelvis and ureter. In addition, we detected the methylation level and mRNA expression of target gene in 8 bladder cancer cell lines and 1 normal bladder epithelial cell line by MSP, qMSP and qPCR. Results: Methylation marker DMRTA2 had a sensitivity of 85.7%, an AUC value of 0.924, and an accuracy of 90.6%. The specificity, from a control group consisting of patients with lithangiuria, prostatoplasia, and prostatitis as well as healthy individuals, is 93.9% (138/161). Notably, the methylation assay had the highest sensitivities for tumors at stages of T1 (94.4%) and T2 (96.6%) compared with T3 (80.0%), T4 (71.4%), and unknown stage (90.0%). While methylation was observed in 34/45 urine samples from patients with carcinomas of renal pelvis and ureter, a good sensitivity of 75.6%, it was detected at extremely low rate of 7.5% (6/80) in those with interfering cancers of kidney and prostate. Additionally, the assay specificity was significantly affected by the age of the cancer patients and selection of healthy controls, critical aspects to be carefully considered during the design and development phase of the methylation-specific testing. Compared with SV-HUC-1, the normal bladder epithelial cell line, DMRTA2 gene was hypermethylated in 8 bladder cancer cell lines, which is consistent with the results of MSP and qMSP. The mRNA levels of DMRTA2 were low in some bladder cancer cell lines, such as T24, J82, UM-UC-3 and RT4, however were fairly high levels in 5637, SCaBER, TCCSUP and SW780. Conclusions: Our data demonstrated that a single-target DNA methylation signature could be highly effective to detect bladder cancer via urine samples.
A phase 1b, open-label, single-arm study of cofetuzumab pelidotin (a PTK7-targeting antibody-drug conjugate) in patients with PTK7-expressing, recurrent non-small cell lung cancer (NSCLC).
Authors: Eric S. Schaefer, D. Ross Camidge, Kiyotaka Yoh, Alona Zer, Tatiana Hernandez Guerrero, Jair Bar, Yusuke Okuma, Julio Antonio Peguero, Maria De Miguel, Mor Tal Moskovitz, Daniel Morgensztern, Shawn Jeffries, Lan Wang, Satwant Lally, Christopher Conn, Xiaohua Xin, Edwin E. Jeng, Melissa Lynne Johnson
Journal: Journal of Clinical Oncology (2021)

TPS3142 Background: Protein tyrosine kinase 7 (PTK7) is a highly conserved receptor tyrosine kinase involved in the Wnt signaling pathway and is overexpressed in multiple cancer types, including non-small cell lung cancer (NSCLC). Cofetuzumab pelidotin (ABBV-647) is an anti-PTK7 antibody-drug conjugate comprising the hu6MO24 monoclonal antibody, a cleavable cysteine-reactive linker, and Aur0101 (an auristatin microtubule inhibitor). It has shown promising preclinical anti-tumor effects (Damelin et al. Sci Transl Med 2017;9[372]:eaag2611) and clinical activity with a manageable safety profile in a Phase 1 study in patients with advanced solid tumors, with promising anti-tumor activity noted in NSCLC (Sachdev et al. DOI: 10.1200/JCO.2018.36.15_suppl.5565). Methods: This open-label, single-arm, multicenter Phase 1b study (NCT04189614) will assess the anti-tumor activity and safety of cofetuzumab pelidotin in approximately 40 patients with PTK7-expressing, recurrent NSCLC. The primary objective is to assess the objective response rate of cofetuzumab pelidotin according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary objectives include the duration of response, progression-free survival, overall survival, and safety and tolerability. Pharmacokinetic and biomarker samples will also be collected throughout for analysis. Patients must be aged ≥18 years with an Eastern Cooperative Oncology Group performance status of 0–1 and have recurrent histologically confirmed NSCLC with PTK7-expressing tumor (using a validated immunohistochemistry assay). Patients must have progressed after treatment with a platinum-based chemotherapy doublet and an immune checkpoint inhibitor (for tumors without targetable genetic alterations), or a platinum-based chemotherapy doublet and targeted agent(s) (for tumors with targetable genetic alterations). Patients must also have received ≤2 prior lines of systemic therapy (≤3 prior lines for tumors treated with targeted agent[s] for genetic alterations), including no more than 1 line of systemic chemotherapy. Cofetuzumab pelidotin (2.8 mg/kg) is administered intravenously every 3 weeks until the patient experiences disease progression, intolerable toxicity, or other study treatment discontinuation criteria are met. The study commenced on February 13, 2020 and enrollment is ongoing. Clinical trial information: NCT04189614.
Retrospective world-wide registry on the efficacy of immune checkpoint inhibitors in alveolar soft part sarcoma: Updated results from sixty patients.
Authors: Nadia Hindi, Evan Rosenbaum, Emily Jonczak, Rainer Hamacher, Piotr Rutkowski, Anthony Skryd, Elizabeth Connolly, Jean-Yves Blay, Antonio Gutierrez, Carolina Bogefors, Hans Gelderblom, Kjetil Boye, Clemence Henon, Javier Martinez-Trufero, Jose A. Lopez-Martin, Andrés Redondo, Claudia Valverde, Bruno Vincenzi, William D. Tap, Javier Martin Broto
Journal: Journal of Clinical Oncology (2021)

11564 Background: Alveolar soft-part sarcoma (ASPS) is a highly metastasizing ultra-rare sarcoma subtype, frequently affecting young adults. Conventional cytotoxic drugs are not effective in ASPS, but antiangiogenics demonstrated significant improvement in tumor burden reduction and PFS in the only ever conducted comparative trial. Immune check-point (PD-1/PD-L1) inhibitors (ICI) are emerging promising drugs in the therapy of ASPS, from small reported retrospective and prospective series. A world-wide registry has been set up with the aim of exploring the efficacy of ICI in ASPS. Methods: Data from adult patients (pts) diagnosed with ASPS and treated with PD- 1/PD-L1 inhibitors for advanced disease in expert sarcoma centers from Europe, Australia and US was retrospectively collected. IRB approval was obtained. Demographics, data related to treatments and outcome were considered. Radiologic assessment was based on RECIST 1.1. Progression-free (PFS) and overall survival (OS) were calculated with Kaplan-Meier method. An updated analysis of this series is presented here. Results: Sixty ASPS pts (27 female/33 male) with a median age at diagnosis of 25y (range 3-61) were registered. Primary tumor arose in limbs in 47 pts (78%) and 41 pts (68%) were metastatic at diagnosis. 52/60 pts (87%) had received previous systemic therapy (including chemotherapy in 19 pts and antiangiogenics in 47pts), with a median of one previous line (0-6). All pts received ICI for metastatic disease. Immunotherapy regimens consisted of monotherapy in 31 pts (52%) and combination in 29 pts (48%) (23 with an antiangiogenic agent). 29/60 pts (48%) received ICI within a clinical trial. Among the 52 evaluable pts, there was 1 complete response (CR) and 20 partial responses (PR) (ORR 40.4%). After a median follow-up of 21 months -mos- (range 4-59), 37/60 pts have progressed to ICI, with a median PFS of 13.4 mos (95% CI 10.1-16.7). Eleven pts received a subsequent line of ICI with a median PFS of 26 mos (95%CI 0-57). 16 pts have died, being the median OS from ICI initiation 38 mos (95% CI 33-43). The 12-mos and 24-mos OS rates were 94% and 70% respectively. Conclusions: This registry constitutes the largest available series of ASPS treated with immune check-point inhibitors. Our results suggest that treatment with ICI provide long-lasting disease control and prolonged OS in pts with advanced ASPS, an ultra-rare entity with limited active therapeutic options. The results on subsequent ICI lines suggest a lack of cross-resistance among different ICI therapies.
Site of service trend and chemotherapy costs of commercial insured patients in 2020 compared to 2014.
Authors: Rogelio Alberto Brito, Kevin Hastings, Elisea Avalos-Reyes
Journal: Journal of Clinical Oncology (2021)

e18858 Background: Over the past decade, chemotherapy site of service has shifted from the physician’s office setting to the hospital outpatient setting. This trend has led to a concern that cancer care costs increase when patients are administered chemotherapy in the hospital outpatient setting (H) compared to a physician’s outpatient office setting (O). In 2014, we published data on the impact of site of service and chemotherapy costs. The purpose of this study is to evaluate the site of service trend and cost differential in a Commercial Insured (CI) population over time. Methods: We examined (CI) claims paid for chemotherapy by a large national payor from February 2019 through January 2020 for breast, colon, and lung cancer (BCL) patients. We then compared these changes to our July 2013 through June 2014 chemotherapy paid claims for BCL patients. Results: From February 2019 through January 2020, paid chemotherapy claims for approximately 23,000 unique patients with BCL had an increase of 23% from 2014. For all patients receiving chemotherapy with BCL, 56% received chemotherapy in the H setting and 44% received chemotherapy in the O setting. This was a significant shift from 2014 where 24% received chemotherapy in H and 76% in O settings. In 2020, the chemotherapy allowable reimbursement share was 67% for H and 33% in the O, a change from 2014 where the chemotherapy allowable reimbursement share was 34% in H and 66% in O. The overall cost per patient increased 57% from 2014 to 2020. When examining costs per patient by site of service, there was a statistically significant increase in H costs from $35,460 to $45,273 (p &lt; 0.0001) per patient and a statistically significant increase in O costs from $21,577 to $28,270 (p &lt; 0.0001) per patient treated in 2014 compared to 2020. Conclusions: In this study, the majority of BCL patients received chemotherapy in the H; this trend has led to substantially higher costs of care for patients treated with chemotherapy in the H compared to the O. Future studies are needed to determine the impact of clinical characteristics, genetic factors and treatment choice on these differences.
Validation of FAPi PET biodistribution by immunohistochemistry in patients with solid cancers: A prospective exploratory study.
Authors: Christine Mona, Matthias R. Benz, Firas Hikmat, Tristan Grogan, Katharina Lueckerath, Ali A Razmaria, Rana Riahi, Roger Slavik, Mark D Grigis, Giuseppe Carlucci, Kimberly A Kelly, Johannes Czernin, David D Dawson, Jeremie Calais
Journal: Journal of Clinical Oncology (2021)

3066 Background: Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts (CAF), a major component of tumor stroma, confer treatment resistance, promote local progression, metastasis and immunosuppression. Because FAP is selectively expressed in the tumor stroma of many cancers, radiolabeled small molecule ligands targeting FAP are being explored for their use as pan-cancer theranostic agents. The objective was to establish the spectrum of FAP expression across various cancers by immunohistochemistry (IHC) and to explore whether 68Ga-FAPi-46 PET image biodistribution faithfully reflects tumor FAP expression from resected tumor and non-tumor specimens. Methods: This study was a prospective, exploratory, imaging trial in cancer patients. Referred volunteer patients scheduled to undergo surgical resection of the primary tumor and/or metastases were eligible. Patients underwent one whole body 68Ga-FAPi-46 PET/CT scan. Subsequently, patients underwent surgical resection of the primary tumor and/or metastasis. The outcome measure was the correlation of 68Ga-FAPi-46 PET maximum standardized uptake value (SUVmax) with FAP IHC score in patient-matched cancer and non-cancer tissue. Results: The frequency of FAP expression across 14 cancers on tissue microarrays ranged from 25 to 100% (mean 76.6±25.3%). For imaging and IHC correlation, fifteen patients with the following cancer types were prospectively included: colorectal (n = 4), head and neck (n = 3), pancreas (n = 2), breast (n = 2),stomach (n = 1), esophagus (n = 2) and uterus (n = 1). All 15 patients underwent surgery following their 68Ga-FAPi-46 PET scan within a mean time interval of 16.1±14.4 days (range 1 – 50 days). For two patients the tumor was deemed unresectable. 68Ga-FAPi-46 SUVmax and IHC scores were higher in cancer tissue than in normal tissue: mean 68Ga-FAPi-46 SUVmax 7.4±4.6 (range 1.5-15.9) vs 1.6±1.2 (range 0.4-5.1), (p &lt; 0.001) and mean FAP IHC score 2.38±0.65 vs 0.54±0.66 (p &lt; 0.001), respectively. The FAP IHC scores strongly correlated with 68Ga-FAPi-46 SUVmax (p = 0.001, repeated measures correlation r = 0.85 (95% CI 0.53-0.95), p &lt; 0.001). Conclusions: 68Ga-FAPi-46 PET biodistribution across multiple cancers strongly correlates with FAP tissue expression as measured by IHC. This translational validation paves the way for large scale prospective trials on the use of 68Ga-FAPi-46 PET/CT as a biomarker and stratification tool for FAP-targeted therapies. Clinical trial information: NCT04147494.