tbuckley/cabot-search huggingface dataset:
Safety and efficacy of direct oral anticoagulants in the treatment of venous thromboembolism in cancer patients: A meta-analysis of randomized controlled trials.
Authors: Muhammad Husnain, Irbaz Bin Riaz, Farva R. Gondal, Safi U. Khan, Anum Riaz, Saad Malik, Gilberto Lopes
Journal: Journal of Clinical Oncology (2018)

e18699 Background: Treatment of venous thromboembolism (VTE) in cancer patients is a challenge due to the high risk of recurrence and bleeding. Low molecular weight heparin has been the standard of care for these patients. Recently two randomized controlled trials accessed the efficacy and safety of direct oral anticoagulants (DOACs) for treatment of VTE in cancer patients. The aim of this meta-analysis is to pool all the data from randomized controlled trials to access the efficacy and safety of DOACs in cancer patients. Methods: A systematic literature search was performed to identify randomized controlled trials studying the role of DOACs versus LMWH or warfarin for the treatment of VTE. We identified the subgroup of cancer patients with VTE treated with DOACs in these trials. We did a meta-analysis of all cancer patients with VTE with CMA-III. Primary endpoint was recurrent VTE and secondary endpoints were any major episode of bleeding and or clinically relevant non major bleeding episode (CRNMB) and all-cause mortality. A subgroup analysis of DOACs versus LMWH was done for both the primary and secondary endpoints. Results: We identified eight RCTs with 2568 cancer patients. 1275 patients were treated with DOACs and 1293 patients were treated with either vitamin K antagonists (VKA) or low molecular weight heparin (LMWH). VTE recurrence rate was significantly lower in the DOACs group 4.7% versus VKA/LMWH group 7.1 % with HR: 0.67, 95% CI: 0.49-0.91, P: 0.01. There was no statistically significant difference in the risk of major bleeding/CRNMBs rate 18.9% in the DOACs group versus 13.45% in the VTE/LMWH group (HR: 1.26, 95% CI: 0.89-1.79, P:0.20). There was no statically difference in all-cause mortality between the two groups (HR 1.02, 95% CI 0.90-1.16, P: 0.77). Subgroup analysis of DOACs vs LMWH failed to show any significant difference between two groups. Conclusions: DOACs are associated with decreased risk of VTE recurrence with out significant increased risk of bleeding in cancer patients with VTE. As there was no difference in mortality and degree of bleeding is similar, patients with cancer can be treated with DOACs as an alternative to VKA/LMWH.
TCT-788 Relationship between total CK, CK-MB, SCAI, and Universal Definition in determining peri-PCI Myocardial Infarction: analysis from the Randomized BIONICS Trial
Authors: Ori Ben-Yehuda, M. Ozgu Ozan, Shmuel Chen, David Kandzari, Pieter Smits, Maayan Konigstein, Martin Leon, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
EFIRM liquid biopsy (eLB)<i>: D</i>etection of ultra-short circulating tumor DNA (usctDNA) in plasma and saliva of non-small cell lung cancer (NSCLC) patients.
Authors: Feng Li, Fang Wei, Wei Liao, Wei-Lun Huang, Chien-chung Lin, David Chia, Charles Strom, Michael Tu, Yong Kim, Wu-Chou Su, David T. Wong
Journal: Journal of Clinical Oncology (2018)

e24062 Background: We previously demonstrated Electric Field-Induced Release and Measurement (EFIRM)-based liquid biopsy (eLB) can detect two frontline actionable EGFR mutations in plasma and saliva from NSCLC patient with 94%-100% concordance to biopsy-based genotyping. Broad scope applications of eLB necessitates mechanistic elucidations of how the EFIRM platform surpasses PCR or NGS-based technologies for the direct detection of ctDNA in micro volume samples. Methods: We obtained the following samples from NSCLC patients: Paired plasma and saliva (n = 13) and malignant pleural effusion (MPE) (n = 21). A side-by-side comparison of EFIRM and ddPCR for the detection of two front line sensitizing actionable EFGR mutations was performed. The correlation among mutation presence in the three bio-fluids was investigated. In addition, pair-end next generation sequencing analysis with affinity capture method targeting EGFR p.L858R ctDNA was employed to determine the size distribution of ctDNA containing mutations in plasma and saliva of NSCLC patients. Results: EFIRM detected L858R and exon 19del mutations equally well in both NSCLC plasma and saliva, while ddPCR detect EGFR mutations with high concordance only in plasma. This led us to the discovery that there are EGFR ctDNA molecules that are PCR-non-amplifiable, which can only be detected by EFIRM. In addition to what has been reported as inter-nucleosome 140-160-bp ctDNA fragments, we found significant representation of the EGFR L858R ctDNA as ultra-short ctDNA (usctDNA) ranging from 40-80bp in plasma of NSCLC patients. In saliva of NSCLC patients, all EGFR L858R ctDNA detected are < 80bp. Examination using cell lines and patient bio-fluids also demonstrated that the majority of usctDNA fragments are localized in the exosomal fraction. Conclusions: Our study demonstrates the existence of exosomal usctDNAs of size smaller than 80bp in patient plasma and saliva. These ultra-short fragments are efficiently detected by EFIRM, not by ddPCR, constituting the scientific basis for the advantage of eLB over other liquid biopsy platforms.
NAMPT expression in stage I/II pancreatic ductal adenocarcinoma.
Authors: Katelynn Davis, Craig Dunseth, Sarah L Mott, Andrew Bellizzi, Carlos Hou Fai Chan
Journal: Journal of Clinical Oncology (2017)

e15735 Background: NAD (nicotinamide adenine dinucleotide), a vital cofactor in redox reactions and a substrate for many enzymes, plays a critical role in cellular metabolism. NAMPT (nicotinamide phosphoribosyltransferase) is a key enzyme that regenerates NAD from its metabolites. NAMPT has been shown to be overexpressed in some cancers, and inhibition of NAMPT in pancreas cancer cell lines and xenografts has been shown to decrease cell growth, making it an attractive potential therapeutic target. Here we correlate NAMPT expression in a large cohort of stage I/II pancreatic ductal adenocarcinomas (PDA) with clinical outcomes and pathologic features. Methods: NAMPT immunohistochemistry (IHC) was performed on tissue microarrays of 250 PDAs. Tumors had been arrayed in triplicate. Each core was evaluated for staining intensity of cancer cells (0 = no staining, 1+ = weak, 2+ = moderate, 3+ = strong), and a mean score was calculated for each case; cases with fewer than 2 cores were excluded. Fisher’s exact and Wilcoxon rank sum tests were used for categorical and continuous variables, respectively. Recurrence-free survival (RFS) and overall survival (OS) differences were evaluated using Cox regression. This study was conducted under an approved IRB protocol. Results: 197 PDAs had at least 2 TMA cores with identifiable cancer cells. The mean IHC score was 0.53 (range 0 to 2.33). While 121/197 PDAs (61%) were positive, only 18/197 (9%) had a score &gt; 1. Stage II tumors had a higher mean score than stage I tumors (0.57 vs 0.31; P = 0.03) and were more likely to be positive (66% of 148 vs 41% of 22; P = 0.03). However, RFS and OS were not significantly different between NAMPT-positive vs NAMPT-negative PDAs. Conclusions: NAMPT expression was detected in 61% of stage I/II PDAs. Frequency and extent of expression correlated with overall stage, suggesting a role in cancer progression. Although NAMPT expression did not correlate with RFS and OS in this study, given its frequent expression in PDA, it represents a potential therapeutic target.
A prognostic model combining CD4/CD8 ratio and N stage predicts the risk of distant metastasis for patients with nasopharyngeal carcinoma treated by intensity modulated radiotherapy.
Authors: Chang-Juan Tao, Yuan yuan Chen, Feng Jiang, xing-Lai Feng, qi-Feng Jin, Ting Jin, yong-Feng Piao, Xiaozhong Chen
Journal: Journal of Clinical Oncology (2016)

6051 Background: Distant metastasis is a poor prognostic factor in nasopharyngeal carcinoma (NPC). We aimed to evaluate the correlation between circulating lymphocyte subsets and clinical variables, and design an effective prognostic model for distant metastasis-free survival (DMFS) in NPC. Methods: Subsets of circulating lymphocytes were determined in 719 non-metastatic NPC patients before treatment, and overall survival and DMFS was monitored. Significant prognostic factors were identified using univariate and multivariate analyses. Results: The percentage of CD19+ lymphocytes correlated negatively with TNM stage (r = –0.082, P = 0.028). Patients with higher CD4/CD8 ratios ( ≥ 1.77) showed better 5-year DMFS than patients with lower ratios (91.9% vs. 85.4%, P < 0.001). Multivariate analysis revealed that CD4/CD8 ratio (HR, 0.450; 95% confidence interval [CI], 0.266–0.760; P = 0.003), T stage (HR, 2.3549; 95% CI, 1.409 – 3.930; P = 0.001) and clinical N stage (HR, 2.294; 95% CI, 1.370 – 3.839; P = 0.002) were independent factors affecting DMFS. The prognostic N-R model we developed divides patients into three groups: (1) low-risk (early N stage and CD4/CD8 ratio ≥ 1.77); (2) intermediate-risk (advanced N stage or CD4/CD8 ratio < 1.77) and (3) high-risk (advanced N stage and CD4/CD8 ratio < 1.77) of distant metastasis. Conclusions: Our prognostic model, based on clinical N stage and CD4/CD8 ratio, may predict the risk of distant metastasis, allowing individualized treatment for NPC.
Patient-reported outcomes in patients with NSCLC who progress on 1st-/2nd-generation EGFR TKIs.
Authors: Karen E Skinner, Ancilla Fernandes, Mark Stephen Walker, Melissa Pavilack, Ari M. Vanderwalde
Journal: Journal of Clinical Oncology (2017)

e20590 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are recommended for patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC). Limited data are available regarding patient-reported outcomes (PROs) in patients who experience progression on 1st-/2nd-generation TKI treatment, which was the focus of this study. Methods: A retrospective chart review of patients with advanced NSCLC (stage IIIb/IV) from 10 US community oncology practices was conducted. Patients were included if they were diagnosed between 1/1/2008 and 1/1/2015, were treated with erlotinib or afatinib (TKIs) either first line (1L) or second line (2L), and had disease progression (per clinician’s assessment) prior to 10/31/2015. Eligible patients with ≥1 Patient Care Monitor record were included in this subset analysis. Linear mixed models were used to evaluate select PROs. Results: The study included 364 patients: 77.7% white, 17.3% African American; and mean (SD) age 66.3 (11.3) years. Of the 241 patients who received systemic anticancer therapies after progression, 33.2% continued on TKIs ± chemotherapy (66.8% chemotherapy alone). PROs were available for 71 of 364 patients. We found that progression was associated with worsening in acute distress, despair, and difficulty breathing ( P&lt; .001, P&lt; .001, P= .048, respectively). Disease progression was also associated with worsening of vomiting and nausea ( P&lt; .001, P= .023, respectively). Patient-reported rash symptoms improved from the TKI treatment period to the post-progression period ( P= .044), which aligned with the incidence of rash in the patient records (61.0% during TKI, 32.9% after progression). Conclusions: As expected, disease progression was associated with worsening of patient psychological symptoms and difficulty in breathing. Interestingly, as disease progressed and patients transitioned from TKI therapies to chemotherapies, there was worsening of vomiting and nausea and a decrease in patient-reported rash symptoms. These findings underscore the need for therapeutic options that improve patient symptomatology after progression on 1st-/2nd-generation EGFR TKIs.
Geriatric assessment to predict toxicity in elderly patients with unresectable locally advanced non-small-cell lung cancer treated with concurrent chemoradiotherapy.
Authors: Ernest Nadal, Jose Carlos Ruffinelli, Ramon Palmero, Arturo Navarro, Maria Plana, Carlos Mesia Barroso, Maria Dolores Arnaiz, Isabel Brao, Monica Arellano, Susana Padrones, Josep Maria Borràs, Felipe Cardenal, Juana Saldana, Maite Antonio Rebollo
Journal: Journal of Clinical Oncology (2018)

8557 Background: There is no consensus on the treatment of elderly patients with unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). We aimed to determine whether the comprehensive geriatric assessment (CGA) as well as other screening tools were able to predict toxicity in this clinical setting. Methods: Elderly patients (≥ 75y) with LA-NSCLC underwent CGA, the Vulnerable Elders Survey (VES-13) screening tool and the Cancer and Aging Research Group (CARG) toxicity predictive tool. Based on CGA, fit and medium-fit patients were deemed candidates for platinum-based chemotherapy concurrent with thoracic radiation therapy (cCRT) and unfit patients received best supportive care. The ability of CGA, CARG and VES-13 to predict grade 3–4 (G3-4) toxicity was assessed by logistic regression. Results: 85 elderly patients with LA-NSCLC were assessed by CGA and classified into fit 37%, medium fit 48% and unfit 15%. Based on VES-13, 56% were considered vulnerable. Fifty-four fit and medium-fit patients received cCRT and 42 (78%) patients completed the scheduled treatment. No differences in treatment completion were seen among both CGA groups. Reasons for not completing cCRT were toxicity (10%), cancer recurrence (4%), patient decision (4%) or aggravation of comorbidities (4%). The median OS (mOS) in fit and medium-fit patients receiving cCRT was 21.1 months (95% CI 16.2 – 26.0). Most common G3-4 adverse events were neutropenia (20%), febrile neutropenia (7.5%), asthenia/fatigue (11%), respiratory infection (13%) and radiation pneumonitis (13%). CARG toxicity tool classified fit and medium-fit patients into high 10%, medium 52% and low risk 38%. GGA groups were not predictive of G3-4 toxicity. Medium and high risk patients based on CARG were more likely to have G3-4 toxicity (p = 0.086).Vulnerable patients defined by VES-13 had significantly higher risk of grade 3-4 toxicity (OR = 3.99, 95% CI 1.28-12.37, p = 0.017). Conclusions: CGA is helpful in selecting elderly patients with unresectable LA-NSCLC that may benefit from cCRT. VES-13 was significantly associated with higher risk of G3-4 toxicity in this clinical setting.
Analysis of PD-L1 and RAD50 in circulating cells recovered from lung cancer patients before and after induction of radiotherapy.
Authors: Daniel L Adams, Martin J. Edelman, R. Katherine Alpaugh, Jianzhong He, Ting Xu, Hui Gao, James M. Reuben, Yawei Qiao, Stephen M. Hahn, Ritsuko Komaki, Zhongxing X. Liao, Cha-Mei Tang, Steven H. Lin
Journal: Journal of Clinical Oncology (2016)

e20537 Background: PD-L1 expression can be altered during radiotherapy (RT) and may be a mechanism for resistance to immunotherapy. In lung cancer (LC), monitoring PD-L1 expression changes in tumor or stroma using repetitive biopsies is not feasible. Sequential tracking of PD-L1 using circulating cells may be a surrogate in assessing marker expression during treatment. RAD50 is a DNA repair gene that can be used to assess tumor cell response to radiation. We sequentially tracked PD-L1 expression and RAD50 induction in 2 cell types (Circulating tumor cells [CTCs] and Cancer Associated Macrophage-like Cells [CAMLs]) in LC patients (pts) before and during RT. Methods: Forty stage I-IV LC pts, receiving radiation/chemoradiation therapy, were included in this prospective pilot study. Baseline blood sample (7.5 ml) was drawn prior to start of RT (T0) and a 2nd sample was drawn at a follow up visit during RT (T1). Blood was processed by CellSiev microfilters; stained for cytokeratin/CD45. Using the QUASR technique, fluorescence signal was removed and cells restained for RAD50 and PD-L1. RAD50 foci numbers within nuclear areas were quantified. PD-L1 intensity was measured and grouped by 4 IHC scores: 0-negative, 1-low, 2-medium, and 3-high. Correlations to pretreatment core biopsy with PD-L1 expression at T0 are being made. Results: At least one cytokeratin positive cell (CTC or CAML) was found in all but 4 samples (95%). CTCs were found in 69% of T0 and 72% of T1 samples and CAMLs in 79% of T0 and 97% of T1 samples. For PD-L1 expression, 12 pts had 0 PD-L1 expression at T0, but increased to > 2 at T1, 15 pts with low PD-L1 expression remained low at T1, and 13 pts with high PD-L1 expression at T0 remained high at T1. RAD50 foci ranged 0-16 per cell, averaging 0.56 at T0, increasing to 4.68 at T1 during RT. No correlation was found between RAD50 induction and PD-L1 expression. PD-L1 expression on core biopsy is ongoing. Conclusions: PD-L1 and RAD50 are quantifiable in CTCs/CAMLs, with an observed correlative response to RT +/- chemotherapy. This data suggests that sequential tracking of CTCs/CAMLs from the primary lung tumor is feasible using microfiltration and may potentially serve as predictive biomarker in cancer therapy.
Abstract 19899: Coffee Consumption is Not Associated With Calcified Atherosclerotic Plaques in the Coronary Arteries: The NHLBI Family Heart Study
Authors: Yash R Patel, Taraka V. Gadiraju, J. Michael Gaziano, Luc Djoussé
Journal: Circulation (2015)

Introduction: The average consumption of coffee per day in the United States is 3.2 cups. While in a recent meta-analysis of 21 prospective studies, coffee consumption was associated with a lower risk of cardiovascular disease mortality, with the lowest risk observed among consumers of 4 cups/day, limited and inconsistent data are available on the relation of coffee intake with subclinical disease. Hypothesis: Our primary hypothesis is that coffee consumption is inversely associated with the prevalence of atherosclerotic plaque in coronary arteries in NHLBI Family Heart Study Methods: In a cross-sectional design, we studied 1929 participants of the NHLBI Family Heart Study without known coronary heart disease. Coffee consumption was assessed by a semi-quantitative food frequency questionnaire and coronary-artery calcium (CAC) was measured by cardiac CT. We defined prevalent CAC using an Agatston score of at least 100 and fitted generalized estimating equations to calculate prevalence odds ratios of CAC. Results: Mean age and BMI were 56.7 years and 28.8 kg/m2 respectively, and 59% were male. In crude analysis, higher coffee consumption was associated with higher prevalence of CAC. Odds ratio (95%CI) for CAC were 1.0 (reference), 1.34 (0.92-1.94), 2.48 (1.81-3.40), 2.45 (1.82-3.30), and 1.81 (1.29-2.56) for coffee consumption of almost never, &lt;1/day, 1/day, 2-3/day, and ≥4 cups/day. However, controlling for potential confounding factors eliminated such association [Corresponding odds ratio (95%CI) for CAC: 0.92 (0.57-1.49), 1.34 (0.86-2.08), 1.30 (0.84-2.02), and 0.99 (0.60-1.64), respectively, adjusting for age, sex, BMI, smoking, alcohol, physical activity, field center, and total calories]. Conclusions: These data do not provide evidence for an association between coffee consumption and prevalent CAC in adult men and women.
cFDNA characteristics in transitional cell carcinoma (TCC) patients who achieved complete response to checkpoint inhibitors (CPI).
Authors: Yen Cao, Mohamed Azab, Subhikshya Tiwari, Mohamad Mubder, Nicholas J. Vogelzang
Journal: Journal of Clinical Oncology (2018)

e16589 Background: cfDNA Transitional Cell Carcinoma patients who achieve complete response (CR) represent a rare population whose disease monitoring with radiographic evaluation remains challenging due to nuances of radiographic findings. In this retrospective study we analyzed the cFDNA characteristics of nine patients who achieved CR with CPI to determine whether there is association between cFDNA fraction and prognosis. Methods: In this retrospective study, we identified 9 patients with TCC who achieved CR correlated to CPI treatment. We describe initial disease staging, treatments received, duration of CR, and cfDNA percent somatic alteration burden (%SAB). Results: Between 6/2015-2/2018 197 solid tumor pts had cfDNA testing in a single practice. 62 had TCC and 21 (14:7 M:F, median age 69) received CPI with cfDNA monitoring. 72 assays (range 1-7/pt) were measured for up to 28 mos (range 2-28 mos). 9 (7:2 M:F) of the 21 CPI treated pts are in clinical CR or near CR (residual radiographic abnormalities of uncertain significance) and are off CPI for 5+ mos. Of these 9 patients, 1 was initially diagnosed with metastatic disease in the bone, while 8 had local disease. While 6 of 9 had disease metastases (2 with bone mets, 3 with lymph nodes, 1 with bone and lymph nodes) with radiographic evaluation at one point of their follow up, all 9 achieved CR. 5 received surgery and 8 failed chemotherapy prior to achieving CR. Of the 9 patients, 6 achieved CR with Atezolizumab, 1 with Pembrolizumab, 1 with Durvalumab, and 1 with Avelumab. Number of therapy cycles ranged from 12-44, with a median of 19. The duration of CR ranged from 2 to 21 months, with a median of 9. At the time of CR evaluation, the %cfDNA for the nine patients were < 0.2 in 7 pts, 0.7 and 0.8 in the remaining 2 patients. Only one patient experienced an increase in %cfDNA following CR. Conclusions: There is an association between %cfDNA and CR, suggesting a role for %cFDNA in disease response to therapy, particularly in CPI. Further prospective studies with larger population are needed to evaluate hypothesis that %cfDNA can be used as a tumor marker.
The correlation between mutation burden and disease free survival in patients with lung adenocarcinomas.
Authors: Changzheng Wang, Shuang Xin, Xulian Shi, Xin Zhao, Kui Wu, Li Zhang, Xiuqing Zhang
Journal: Journal of Clinical Oncology (2017)

8550 Background: Lung cancer is one of the leading causes of cancerous deaths globally. High mutation burden is a special character in lung adenocarcinoma patients. Mutation burden is usually based on the number of non-synonymous mutations implying the instability of genome. We hypothesize genome-wide mutation burden indicates mutation degree and is correlated with prognostic in lung adenocarcinoma. Methods: Whole-exome sequencing was performed on 98 Chinese lung adenocarcinoma patients with tumor and normal tissue to a mean depth of 49.6ⅹ. The total number of non-synonymous somatic mutations was calculated from the sequencing data of each patient. Patients were divided into high mutation burden and low mutation burden groups in accordance with the mean mutation burden and Kaplan-Meier analysis was performed for survival analysis between these two groups. The association between mutation burden and age or smoking status was analyzed by Wilcoxon rank-sum test. Results: Among these 98 patients, the values of mutation burden varied from 5 to 1121 with mean value 161.8, 36 (36.7%) patients with smoking history and 34 (34.7%) patients were older than 65 years; the numbers of patients in I, II, III stage were 19 (19.4%), 16 (16.3%) and 63 (64.3%) respectively. 32 patients were classified into high mutation burden group, the other 66 patients classified into low mutation burden group. Survival analysis showed a significantly longer disease free survival (DFS) in low mutation burden group (p-value = 0.0133).Mutation burden was significantly associated with age ( &lt; 65 vs ≥65, p-value = 0.0208) and smoking status (p-value = 8.67ⅹ10 -4 ). Conclusions: The association between mutation burden and age or smoking status suggested the high risk for mutation burden accumulation. The significant difference of DFS between high mutation burden and low mutation burden groups reveals the potential of mutation burden as one of the prognostic factors in patients with lung adenocarcinomas.