tbuckley/cabot-search huggingface dataset:
Cell free (cf)DNA as a tumor marker in transitional cell carcinoma (TCC).
Authors: Mohamed Azab, Yen Cao, Subhikshya Tiwari, Mohamad Mubder, Chad L Cross, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2018)

e16514 Background: Assessment of tumor response is challenging given the nuances of radiographic findings, especially in bone. cfDNA appears to correlate with tumor burden (GUASCO 2018) and thus has potential as a tumor marker in TCC, particularly in regards to determining complete response (CR) after checkpoint inhibitor therapy (CPI). Methods: This retrospective analysis evaluated 62 patients (pts) with TCC from a single practice. cfDNA were collected along with corresponding radiographic imagings at the same time interval. We correlated between the %cfDNA at each of these time points to the radiographic response of the disease to treatment at the same time point. Radiographic and clinical response were categorized into CR, Incomplete Response (IR), Stable Disease (SD), and Progressive Disease (PD). We ran a non parametric ANOVA based on mean ranks. Results: Between 6/2015-2/2018 197 solid tumor pts had cfDNA testing in a single practice. 62 had TCC and of these, 24 pts (18:6 M:F, mean age 69) had more than one cfDNA testing (2-7) with a total of 47 tests. 14 ,9 ,8 ,16 of these time points were of pts at CR, IR, SD and PD respectively. Of the 9 pts who had CR, 5 received IO (1 Durvalumab, 4 Atezolizumab),2 received chemotherapy (1 MVAC and 1 GEM+CIS), 1 pts received surgery and IO (Pembrolizumab). Median cfDNA% in CR, IR, SD and PD groups were 0.15, 0.1, 0.8 and 3.65 respectively. There is an overall significant difference when comparing the mean rank of the responses ( p= .005). Bonferroni-corrected multiple comparisons showed a significant pairwise difference between CR and PD (p= .02) and between CR and IR (p= .019). Total cfDNA% in the CR group was ND in 4 samples, 0.1 in 3 samples, 0.2 in 3 samples, and 0.5, 1.2, 2.8, 5.1 in the remaining samples. While, total cfDNA% in IR group was ND in 3 samples. 0.1 in 2 samples, and 0.3, 0.5, 0.7, 1.1 in the remaining samples. Total cfDNA% in the PD group was ND and 0.1 in two samples, and 0.6, 0.9, 1.6, 1.9, 5.4, 7.9, 9.8, 10.1, 14.1, 16.1, 28, 28.1 in the remaining sample. Conclusions: The significant difference in cfDNA% in CR vs PD and CR vs IR suggests an association between cfDNA% and tumor response. Further prospective studies with larger sample size are needed to confirm this hypothesis that cfDNA can serve as a marker of molecular CR.
Prognostic value of BAP1 expression in clear cell renal cell carcinoma with inferior vena cava tumor thrombosis.
Authors: Suguru Oka, Naoko Inoshita, Yuji Miura, Ryosuke Oki, Yu Miyama, Shoichi Nagamoto, Kohei Ogawa, Kazushige Sakaguchi, Chihiro Kondoh, Kazuhiro Kurosawa, Shinji Urakami, Toshimi Takano, Toshikazu Okaneya
Journal: Journal of Clinical Oncology (2017)

e16080 Background: Renal cell carcinoma (RCC) is characterized by a propensity for extension into the renal vein and inferior vena cava (IVC), and affected patients have a poor prognosis. BAP1 mutation, which occurs in about 15% of patients with clear cell RCC (ccRCC), also predicts a poor prognosis. The aim of this study was to elucidate the association between BAP1 expression and clinicopathologic outcomes in patients with ccRCC with an IVC tumor thrombus. Methods: Thirty-nine patients with ccRCC with an IVC tumor thrombus who underwent radical nephrectomy and tumor thrombectomy at our institution from 1999 to 2010 were retrospectively evaluated. Immunohistochemical analyses were performed for the expression of BAP1, and the associations between the expression of BAP1 and clinical outcomes were assessed. Survival analyses were performed using the Kaplan–Meier method and log-rank test. Multivariate analyses of the associations between overall survival (OS) and clinical variables were performed using a Cox proportional hazard model. For all analyses, P &lt; 0.05 was considered statistically significant. Results: The median follow-up time was 58.8 months (range, 2–130 months). The median age was 66 years (range, 37–80 years). Four patients (10.3%) had lung metastasis at the initial diagnosis. The primary tumor was right-sided in 27 (69.2%) patients and left-sided in 12 (30.8%). The IVC tumor thrombus extended above and below the diaphragm in 11 (28.2%) and 28 (71.8%) patients, respectively. The KPS score was &gt; 80 in 23 patients (59.0%). BAP1 expression was positive in 26 (67.0%) cases and negative in 13 (33.0%). BAP1-negative tumors were associated with a significantly shorter OS than BAP1-positive tumors (median OS, 42.0 vs. 81.5 months, respectively; P = 0.019). The median disease-free survival in BAP1-negative and -positive tumors was 10.0 and 19.0 months, respectively (P = 0.019). Multivariate analysis showed that only a BAP1-negative status was significantly associated with shorter OS (P = 0.026). Conclusions: A BAP1-negative tumor status was significantly associated with a poor prognosis in patients with ccRCC with an IVC tumor thrombus who underwent radical nephrectomy and tumor thrombectomy.
Circulating tumor DNA dynamics in resectable gastric cancer.
Authors: Alessandro Leal, Nicole C.T. van Grieken, Jillian Phallen, Doreen N. Palsgrove, Vilmos Adleff, Fabienne Warmerdam, Donald L. Van der Peet, Henk M.W. Verheul, D. J. Van Spronsen, Johanna MG Van Riel, Maud Geenen, Johanna Elisabeth A. Portielje, Hanneke W.M. Van Laarhoven, Edwin PM Jansen, Karolina Sikorska, Elma Meershoek – Klein Kranenbarg, Cornelis J. H. Van De Velde, Marcel Verheij, Annemieke Cats, Victor E. Velculescu
Journal: Journal of Clinical Oncology (2018)

4069 Background: There is an unmet need for predictive biomarkers of clinical outcomes in resectable gastric cancer (RGC) treated with perioperative chemotherapy. We have used targeted error correction sequencing (TEC-Seq) to analyze 58 driver genes in cell-free circulating tumor DNA (ctDNA) from patients enrolled in the CRITICS study (NCT00407186). Methods: We prospectively isolated cell-free DNA (cfDNA) from plasma of 115 patients with stage Ib-IVa RGC enrolled in a phase III trial of neoadjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy. Samples were collected prior to neoadjuvant treatment (baseline), as well as prior to and after partial or total gastrectomy. Pathologic responses to neoadjuvant chemotherapy were assessed using tumor regression grade (TRG). Tumor-derived alterations were analyzed using TEC-Seq at the indicated timepoints. Results: Patients had a median follow-up of over 60 months. Initial analyses of 84 plasma samples from 52 patients revealed median levels of cfDNA of 9.8 ng/ml (0.8-123.0). We detected 259 somatic mutations in 34 genes. Patients with tubular adenocarcinoma had higher ctDNA concentrations than signet-ring cell carcinoma at baseline, with median mutant allele fractions (MAFs) of 0.25% vs. 0.16%, respectively (P <0.001). ctDNA levels were reduced after neoadjuvant chemotherapy, with MAFs declining from 0.22% to 0.15% (P <0.001). TRG 1-3 responses were associated with longer median overall survival (OS) (not reached (NR) vs. 39.4 months, HR = 0.23; 95% CI = 0.06-0.96, P = 0.04) and event-free survival (EFS) (NR vs. 33.8 months, HR = 0.34; 95% CI = 0.14-0.96, P = 0.02). We observed a trend for longer OS and EFS among patients with detectable ctDNA at baseline who were treated with perioperative chemotherapy (median OS NR vs. 37.4 months, HR = 0.39; 95% CI = 0.12 to 1.25, P = 0.1; median EFS NR vs. 30 months, HR = 0.53; CI 95% 0.18-1.6, P = 0.2, respectively). Conclusions: Our study shows that ctDNA levels differ between histologic subtypes of gastric cancer. The presence of detectable ctDNA at baseline may provide a predictive real-time biomarker of neoadjuvant chemotherapy benefit in patients with resectable disease. Additional ctDNA analyses at all timepoints will be presented. Clinical trial information: NCT00407186.
Extracellular vesicle-derived miRNA profile for patients with pulmonary ground glass nodule.
Authors: Jia-Tao Zhang, Jian Wu, Fu-Gen Li, Fang Yang, Hao Qin, Jun-Tao Lin, Rui Fu, Ben-Yuan Jiang, Song Dong, Ri-Qiang Liao, Xue-Ning Yang, Yi-Long Wu, Wenzhao Zhong
Journal: Journal of Clinical Oncology (2018)

e24037 Background: Plasma extracellular vesicles have been implicated as a non-invasive diagnostic source. However, little high throughput screening has been done in the early-stage lung cancer and problems such as bias of enrollment, less rigorous identification exists. This study aimed to demonstrate the extracellular vesicle-derived miRNA profile for early-stage lung cancer patients, especially those with ground glass nodule (GGN). Methods: Prospectively collected pre- and postoperative plasma samples from patients with solitary pulmonary nodule, and finally included 5 pure GGNs, 5 mixed GGNs and 5 solid nodules. Extracellular vesicles were collected from 1mL plasma and isolated with 3D Medicine EV isolation kit, then identified by anti-CD9 western blot and transmission electron microscope (TEM). Plasma extracellular vesicles miRNA profiling from these patients and 10 healthy volunteers were performed using miRNA-seq. Results: The significant different miRNA profile has been found between preoperative group and healthy group via cluster analysis and principal component analysis. And the tendency of differentiation has also been observed in three subgroups: pure GGN (size range: 0.8 ∼ 1.6cm), mixed GGN (size range: 0.9 ∼ 2.4cm; solid component size range: 0.4~2.2cm) and solid nodule (size range: 1.1 ∼ 2.4cm). There were 28 up-regulated miRNAs and 6 down-regulated miRNAs in malignant group patients (p < 0.01, fold change > 1.5 or < 0.66). Furthermore, combined the significant expression differences after surgery, two promising miRNAs were identified: miR-374a-5p (down-regulated in malignant group and up-regulated after surgery), miR-320a (up-regulated in malignant group and down-regulated after surgery). Conclusions: The current analysis observed the different miRNA profile from plasma extracellular vesicles between malignant group and healthy group. However, the diagnostic value of extracellular vesicle-derived miRNA for early stage lung cancer remains to be further explored.
TCT-79 Quality of Life in Patients With Refractory Angina After Chronic Total Occlusion Angioplasty
Authors: Taishi Hirai, J. Aaron Grantham, Kensey Gosch, William Lombardi, Dimitri Karmpaliotis, Jeffrey W. Moses, William Nicholson, Adam Salisbury
Journal: Journal of the American College of Cardiology (2018)
Disparities in cancer outcomes across age, sex, and race/ethnicity among pancreatic cancer patients.
Authors: Angela Tramontano, Ryan David Nipp, Chung Yin Kong, Pari Pandharipande, Emily Dowling, Deborah Schrag, Chin Hur
Journal: Journal of Clinical Oncology (2017)

e18071 Background: Age, sex, and racial/ethnic disparities exist for several malignancies, but these relationships are understudied in pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to determine whether these disparities persist in survival and treatment after adjusting for demographic, clinical, and treatment characteristics. Methods: Our study includes PDAC patients (pts) diagnosed from 1992-2011 in the SEER-Medicare database. We used Cox regression models to compare survival across age, sex, and race/ethnicity, stratified by non-metastatic and metastatic cancer. We used logistic regression to compare differences in chemotherapy, radiation, and surgery receipt across age, sex, and race/ethnicity. We adjusted for marital status, urban location, socioeconomic factors, SEER region, comorbidities, cancer stage, lymph node status, tumor location, tumor grade, diagnosis year, and chemotherapy, radiation, and/or surgery receipt. Results: Of 20,896 PDAC pts (median diagnosis age = 75 years; 56% female), 84% were White, 9% Black, 5% Asian, and 2% Hispanic; 53% had metastatic cancer. Among non-metastatic pts, adjusted Cox regression demonstrated that older pts had worse survival compared with younger pts (HR: ≥1.1 for all ages [reference = 66-69 years vs. 70-74, 75-79, 80-84, 85+], p &lt; 0.01 for all); we found no survival differences between sexes. Black (HR: 1.1, p = 0.01) and Hispanic (HR: 1.2, p &lt; 0.01) pts had worse survival compared to White pts. Among metastatic cancer pts, adjusted Cox regression demonstrated that older pts (HR: 1.1 for age 85+ [reference = 66-69 years], p &lt; 0.01) had worse survival than younger pts, and males (HR: 1.1, p &lt; 0.01) had worse survival than females. There were no racial/ethnic differences. There were disparities in treatment received; older age and minority race/ethnicity were associated with lower likelihood of receiving chemotherapy, radiation, and/or surgery. Conclusions: Age, sex, and racial/ethnic disparities in survival outcomes and treatment received exist for PDAC pts; these disparities persist after adjusting for differences in demographic, clinical, and treatment characteristics.
Prognostic value of neutrophil-to-lymphocyte ratio in advanced EGFR-mutated non-small cell lung cancer (NSCLC) treated with a tyrosine-kinase inhibitors: A retrospective analysis in a series of western patients.
Authors: Fausto Meriggi, Claudio Codignola, Giordano D. Beretta, Giovanni Luca Ceresoli, Alberto Caprioli, Mario Scartozzi, Anna Paola Fraccon, Tiziana Prochilo, Chiara Ogliosi, Silvia Noventa, Michela Libertini, Alberto Zaniboni
Journal: Journal of Clinical Oncology (2017)

e23045 Background: Several studies demonstrated that an elevated neutrophil-to-lymphocyte ratio (NLR) correlate with a poor prognosis both in early and advanced stage of NSCLC. The aim of this retrospective analysis was to investigate the correlation between NLR and prognosis in caucasian patients diagnosed with advanced EGFR-mutated NSCLC and treated with tyrosine kinase inhibitors (TKIs). Methods: A retrospective database was used to identify consecutive patients diagnosed with advanced EGFR-mutated NSCLC and treated with TKIs. From January 2011 to December 2015, 63 patients from five Institutions were enclosed in our series. NLR was derived from the absolute neutrophil and the absolute lymphocyte counts of a full blood count.Survival curves were calculated with Kaplan-Meier method and data were compared by log-rank test. Prognostic significance of NLR were assessed using a Cox regression analysis. Results: Sixty-three eligible patients were stratified according to the mean pretreatment NLR value (3.57 ± 2.42). The chosen cut-off for NLR was 3.5. Forty patients had NLR &lt; 3.5 while 23 patients had a value of NLR &gt; 3.5.A statistical significant difference, both in PFS and OS, was found in the NLR &lt; 3.5 group compared with the higher NLR group (PFS: p &lt; 0.01, OS: p &lt; 0.05). According to univariate analysis, histological type (adenocarcinoma vs non-adenocarcinoma) and NLR value correlate significantly with PFS and OS. In Cox multivariate analysis, only NLR ³ 3.5 resulted significantly associated as independent prognostic factor for worse PFS (HR 2.275, 95% CI 1.257-4.116, p &lt; 0.01) and OS (HR 2.699, 95% CI 1.187-6.137, p &lt; 0.05). Conclusions: Pre-treatment NLR seems to represent a reliable, simple, and easy to reproduce, laboratory tool to predict survival and outcome to therapies in western caucasian EGFR-mutated NSCLC patients. Further prospective trials are needed to definitively confirm its prognostic and predictive role.
Correlation of immune infiltration of cytotoxic T cells and activated microglia in glioblastoma (GBM) post anti-PD1 therapy with response.
Authors: Andrew Silverman, Robyn Denise Gartrell, Junfei Zhao, Syeda Sabeeka Batool, Thomas D Hart, Syed Shabee Hasan, James H. Garvin, George Zanazzi, Fabio Massaiti Iwamoto, Raul Rabadan, Peter Canoll, Yvonne M. Saenger
Journal: Journal of Clinical Oncology (2018)

2055 Background: Glioblastoma (GBM) is an aggressive malignancy of the central nervous system with an abysmal prognosis. Recent advances in immunotherapy, including anti-programmed cell death-1 (anti-PD1), has shown potential to improve outcomes for some GBM patients. In this study, we evaluate the immune cell densities in post-treatment biopsies from patients treated with anti-PD1 for refractory GBM. We hypothesized that density of both cytotoxic T lymphocytes (CTLs) and activated microglia is higher within the tumor mircro-environment (TME) in patients who respond to anti-PD1. Methods: Formalin-Fixed, Paraffin-Embedded (FFPE) tumor samples from a preliminary cohort of five patients with GBM, 2 non-responders and 3 responders, were stained using quantitative multiplex Immunofluorescence (qmIF). Response was classified as decrease in tumor volume by > 50% and/or survival for 6 months without growth of tumor by > 25%. Stains were sequentially applied, using Opal multiplexing/qmIF for CD3 (T cells), CD8 (cytotoxic T lymphocytes (CTLs)), FOXP3 (regulatory T cells – Tregs), CD68 (microglia), HLA-DR (immune activation/tumor presentation), and SOX2 (tumor marker). Multispectral images (MSIs) were acquired using Vectra and analyzed using inForm software and R studio to evaluate density of immune phenotypes within the TME. Results: We find that post-treatment, the patents who responded to anti-PD1 have a significantly increased CTL/total cell density (p = 0.0393) and higher activated microglia CD68+HLA-DR+/ total CD68 density (p = 0.0208), when compared to non-responders. Tregs were rarely seen in either subset of patients and had no significant correlation with response. Conclusions: Preliminary analysis demonstrates higher CTLs and activated microglia in the TME after treatment in patients with GBM who responded to anti-PD1 therapy. Analysis of a larger cohort of 17 patients with specimens at baseline, recurrence and post anti-PD1 is underway and will be presented at the meeting. This data would confirm that anti-PD1 can induce increased inflammation within the TME in GBM despite the blood brain barrier and suggest that further alteration of the immune TME may improve outcomes in GBM.
Glypican-5 to suppress NSCLC metastasis and EMT process by blocking Wnt/β-catenin signaling pathway.
Authors: Mantang Qiu, Jie Wang, Wenjia Xia, Siwei Wang, Gaochao Dong, Rong Yin, Lin Xu, Youtao Xu, Xin Yang
Journal: Journal of Clinical Oncology (2016)

e23014 Background: Non-small cell lung cancer (NSCLC) is a highly aggressive tumor and metastasis is a critical challenge of oncologist. Identification of key genes involved in the process of metastasis is urgent for early detection and treatment of NSCLC. Methods: Expression of Glypican-5 (GPC5) in NSCLC and normal tissues were analyzed by qRT-PCR and tissue microarray. Immunoprecipitation (IP) was performed to the interaction between GPC5 and Wnt3a. Results: GPC5 was significantly downregulated in NSCLC tissues compared with adjacent normal tissues and low GPC5 expression indicated poor survival of NSCLC patient. GPC5 expression in the lymph node metastasis group was remarkably lower than that in the non-metastasis group. RNA sequencing showed that GPC5 restoration led to decreased expression of genes associated with Wnt pathway and epithelial-mesenchymal transition (EMT) process, such as Vimentin, Twist1, Snail1, and MMP2. Both in vitro and in vivo experiments showed restoration of GPC5 expression in NSCLC cell lines inhibited metastasis and blocked TGF-β induced EMT. IP assay demonstrated that overexpression of GPC5 could completely bind with Wnt3a and block β-catenin in the cytoplasm. Conclusions: We demonstrated that GPC5 is a potential tumor suppressor in NSCLC and suppresses metastasis by blocking Wnt/β-catenin pathway.
Abstract 13419: Linear Fractional Shortening on Echocardiography (Echo)- A Novel Index of Right Ventricular Systolic Dysfunction as Validated by Cardiac Magnetic Resonance (CMR)
Authors: Aparna Srinivasan, Jiwon Kim, Melissa Rusli, Attila Feher, Alexi Geevarghese, Antonino Di Franco, Saadat A Khan, Tara Shah, Meenakshi Rozenstrauch, Omar Khalique, Richard B Devereux, Jonathan W Weinsaft
Journal: Circulation (2016)

Introduction: Among pts with LV systolic dysfunction (LV dys ), biventricular (LV and RV) dysfunction (BiV dys ) impacts outcomes. Echo linear indices are widely used to assess LV dys but performance for RV dys is unknown. Methods: The population comprised LV and BiV dys pts (gender, BSA matched) undergoing echo and CMR within 2 weeks: Echo included standard RV indices (fractional area change [FAC], TAPSE, S’) and linear fractional shortening (FS) in parasternal (RV outflow tract [RV OT ]) and apical 4 chamber views (width [RV WD ], length [RV LG ]). CMR was the reference for volumetric LV &amp; RV dys (EF&lt;50%): Linear echo cutoffs were first established in a derivation cohort; then tested in a validation cohort. Results: 168 pts (67% M, 57±15 yo) underwent echo and CMR (3±3 days); BiV dys pts had lower RVEF (36±9 vs 58±6%) and LVEF (28±12 vs 37±9%, both p&lt;0.001) on CMR. On echo, FAC (47±9 vs 28±11), TAPSE (1.9±0.4 vs 1.5±0.3) and S’ (11.4±2.3 vs 9.9±2.6, all p&lt;0.001) were lower with BiV dys , as were all linear FS indices (RV OT 32±8 vs 17±10
A randomized, double-blind, placebo-controlled, multi-centered phase 3 trial comparing fruquintinib versus placebo plus best supportive care in Chinese patients with metastatic colorectal cancer (FRESCO).
Authors: Jin Li, Shukui Qin, Yuxian Bai, Yanhong Deng, Lei Yang, Rui-hua Xu, Zhendong Chen, Haijun Zhong, Hongming Pan, Yongqian Shu, Ying Yuan, Nong Xu, Jianfeng Zhou, Tianshu Liu, DONG MA, Changping Wu, Ying Cheng, Songhua Fan, Ye Hua, Weiguo Su
Journal: Journal of Clinical Oncology (2017)

3508 Background: Treatment options for third-line metastatic colorectal cancer (mCRC) patients remain limited in China. Fruquintinib, an oral kinase inhibitor selectively targeting vascular endothelial growth factor receptors, in a phase II study was found to significantly improve progression free survival (“PFS”) in patients with mCRC as compared to placebo (ESMO abs#2111). Based on these results, a Phase III registration trial, FRESCO, was carried out to confirm fruquintinib’s efficacy and safety in third-line mCRC patients (clinicaltrials.gov # NCT02314819). Methods: This is a randomized, double-blind, placebo-controlled, multi-center phase III trial. Patients with mCRC who have failed at least 2 lines of systemic chemotherapy were enrolled from 28 centers in China. Patients were stratified based on prior anti-VEGF therapy and K-ras status and randomized to a fruquintinib or placebo arm in a 2:1 ratio. The primary endpoint was overall survival (“OS”) which was analyzed in the intent-to-treat population. Results: Between December 12, 2014 and May 13, 2016, 416 patients were randomized. Protocol predefined number of OS events for final analysis was reached on January 17, 2017. Fruquintinib significantly improved OS comparing to placebo with a hazard ratio of 0.65 (95% CI: 0.51-0.83; two sided p&lt;0.001). Median OS was 9.30 months [95% CI 8.18-10.45] in the fruquintinib group versus 6.57 months [95% CI 5.88-8.11] in the placebo group. Statistically significant benefits were also seen with fruquintinib in all secondary endpoints, such as PFS, objective response rate and disease control rate. The most frequent fruquintinib-related ≥ Grade 3 treatment emerged adverse events included hypertension (21.6%), hand-foot skin reaction (10.8%), proteinuria (3.2%) and diarrhea (3.2%). Conclusion: In this phase III confirmatory trial, fruquintinib demonstrated a statistically significant and clinically meaningful OS benefit as compared with placebo in mCRC patients in China. Fruquintinib was well tolerated with a safety profile that is consistent with what was reported previously. Clinical trial information: NCT02314819.