bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptional characterization of immune microenvironment and their prediction role for the prognosis of local advanced lung adenocarcinoma.
Authors: Chen Yuqiao , Shi Xinying , Song Xue , Gao Lingling , Mao Beibei , Zhang Henghui , Zhou Yuan , Zhuang Wei 
Published: May 2019

e20625 Background: The resection of early stage NSCLC offers patients the best hope of a cure. However, the recurrence rate post-resection remains high. As the mechanisms involved in the process is still not clear due to the unavailability of accurate targets, our study was aimed to integrate the impact of different immune context present in lung adenocarcinoma (LUAD) microenvironment on patients’ prognosis. Methods: RNA targeted sequencing was performed on 24 primary tumor specimens from the resected local advanced LUADs . Transcripts of 395 immune related genes expressed in FFPE tumor samples were analyzed. The limma package was used to analyze the different expressed genes (DEGs) between patients with different prognosis. The gene set variance analysis (GSVA) analysis was performed to explore gene sets enrichment related to the prognosis (PFS, progression free survival) post-resection. Results: 23 DEGs were detected in primary tumor between the better (PFS > 18months, n = 12 ) and worse (PFS≤18months, n = 12 ) prognosis group. The combined prediction model containing MPO, IL-6, CXCR2, FCGR3B, ADGRE5 could identify the favorable prognosis of patients. GSVA and Log Rank test of survival data demonstrated that the antigen processing and lymphocyte activation pathway enrichment may associate with better prognosis (p = 0.01), whereas higher Neutrophils cell infiltration in primary tumor demonstrated a shorter PFS (p = 0.008). Conclusions: In LUAD, the immune related genes such as MPO, IL-6, CXCR2, FCGR3B, ADGRE5, can effectively profile the landscape of tumor immune microenvironment and predict the survival in early stage of lung adenocarcinoma. Accordingly immune pathways were correlated with prognosis of these patients. Our findings suggest that immune-related RNA expression pattern in locally advanced LUAD may provide a potential predictive marker for early recurrence after surgical resection.
Neutrophils lymphocyte ratio role in predicting response to checkpoint inhibitors in metastatic non-small lung cancer.
Authors: Hakim Hosam , Abdalla Ahmed , Hadid Tarik H. 
Published: May 2019

e20646 Background: There have been numerous advances in the management of metastatic lung cancer, including targeted therapy against certain mutations in cancer cells and later developing immune therapy with check point inhibitors.From the pre-immune therapy era, a simple blood test allowing the calculation of the neutrophil-to-lymphocyte ratio (NLR) was established as a strong prognostic marker associated with worse overall survival (OS) in several tumor types including non-small cell lung cancer (NSCLC). Methods: We have retrospectively reviewed electronic medical records for patients with Metastatic NSCLC whom received at least one dose of Checkpoint Inhibitors from January 2014 till January 2019 in Van Eslander Cancer Center.The analysis was done using SPSS v. 25.0 and a p-value of 0.05 or less was considered to indicate statistical significance. A univariant analysis was done using Student’s t-test, the Mann-Whitney U test and the chi-squared test. Survival analysis was conducted using Kaplan Meier methodology as well as Cox proportional hazards models. Results: There were 80 patients with metastatic NSCLC received at least one dose of a checkpoint inhibitor. Median age was 63.9 ± 9.3; Males were 45%; Whites were 62.5%. 67.5% of patient had adenocarcinoma and 24% had squamous cell carcinoma. Twenty patients had brain metastasis (25%) and nineteen patients had liver metastasis (24.6%). Eleven patients (13.8%) had PDL-1 greater than 50% and 11 patients (13.8%) had PDL-1 between 1%-50% and 22 patients (27.5%) had negative PD-L1 status. 18.8% received immunotherapy as a first-line treatment and 65% got immunotherapy on their second line and 16.3% had immunotherapy as the third line of treatment or more. Sixty-one patients (76.2%) received Nivolumab and nineteen patients (23.8%) received pembrolizumab. Mean duration of immunotherapy was 13.7 months ± 20.7. Mean NLR was 6.1 ± 5. Patient with NLR > 5:1 had statistically significant higher progression-free survival (PFS) 27.5 months compared to 12 months P = 0.02. Also, Patients with baseline NLR > 5:1 had a trend toward higher median overall survival (OS) but was not statistically significant 41 months compared to 12 months P = 0.08. Conclusions: Our data showed similar finding to Bagley et al and other retrospective analysis from multiple institutes showing that NLR could be a good predictor of response to checkpoint inhibitors And a cutoff of NLR higher than 5.1 was associated with statistically significant better PFS and a trend towards a better OS.
Immune related adverse events in NSCLC patients treated with immune checkpoint therapy who received the influenza vaccination versus no vaccination.
Authors: Reddy Haritha G. , Weis Taylor Mai , Hough Shannon , Daignault Stephanie , Schneider Bryan J. 
Published: May 2019

e20657 Background: Influenza vaccination is recommended by the CDC for cancer patients to reduce the risk of influenza-related complications. There is concern that the incidence of immune-related adverse events (irAEs) may be greater in vaccinated patients receiving immune checkpoint inhibitors (ICPI). We sought to interrogate if influenza vaccination in patients with NSCLC receiving ICPI therapy had an increased incidence of irAEs compared to non-vaccinated patients. Methods: We conducted a single-center retrospective analysis of patients with advanced NSCLC who received PD-1 or PD-L1 inhibitor monotherapy between 3/2015 – 12/2018. Influenza immunization records from both institutional and state-wide registries were obtained from 2014 -2019. Comparisons of adverse event incidence between flu vaccinated and control patients were tested using chi-square statistics. Results: 117 patients were included in our analysis, 33 (28%) were vaccinated during ICPI therapy, 19 (58%) received quadrivalent influenza vaccine, 13 (39%) received trivalent influenza vaccine and 1 (3%) was undetermined. 22 (67%) vaccinated patients had an irAE vs 53 (63%) patients who were not vaccinated during ICPI therapy (p = 0.720). 8 (24%) vaccinated patients had an irAE leading to discontinuation of therapy vs 12 (14%) patients who were not vaccinated during ICPI therapy (p = 0.198). The most frequent irAE in both groups was fatigue 16 (48%) vs 28 (33%) (p = 0.128). Notable irAEs included colitis (0 vs 1), pneumonitis (3 vs 3), hepatitis (1 vs 4) in vaccinated patients vs without vaccine, respectively. There were no statistically significant differences in baseline demographics between both groups including age, race, gender, tumor histology or ECOG performance status. Conclusions: Our study suggests that irAEs are not significantly increased with vaccination for influenza during ICPI therapy. However, there is a slight trend toward increased incidence of irAE warranting ICPI discontinuation for which further investigation is needed. Limitations of this study include a small sample size and inability to grade irAE retrospectively.
NTRK1 fusion identified by capture-based next-generation sequencing in non-small-cell lung cancer.
Authors: Zhao Ruiying , Xiang Chan , Dong Nan , Guo Lianying , Ma Shengji , Han Yuchen 
Published: May 2019

e20664 Background: The clinicopathological features and genomic rearrangements of neurotrophic tyrosine kinase receptors (NTRKs) fusion in non-small-cell lung cancer (NSCLC) have not been fully identified. To explore NTRK1 fusion in non-small-cell lung cancer (NSCLC) specimens, and to explore the relationships between the NTRK1 fusion and the clinicopathological features and to identify genomic rearrangements by multiple molecular methods. Methods: In total, 3947 NSCLC specimens were tested for NTRK1 fusion using genomic DNA capture-based NGS. Then, these NTRK1 fusion cases were identified by Oncomine Focus Assay and FISH. The clinicopathological features were analyzed. Results: In total, five specimens (0.13%) were detected NTRK1 fusion. All these five specimens were adenocarcinoma (0.15%, 5/3423), while no NTRK1 fusions were found in 496 squamous cell carcinoma (SCC) cases and 28 adenosquamous carcinoma (ASC) cases. The ages of patients carried NTRK fusion were range from 31-year to 64-year-old. These five NTRK1 fusion cases were two females and three males, four non-smokers and one with 30 years smoking history, three surgical specimens and two small biopsies. Among these three surgical specimens, one was minimally invasive adenocarcinoma and two were invasive adenocarcinoma. One canonical fusion (TPM3-NTRK1) was detected, the other four were noncanonical fusion type (C14orf2-NTRK1, RRNAD1-NTRK1, LOC101060524-NTRK1, ARHGEF11-NTRK1). The RRNAD1-NTRK1 case was coexist with L858R mutation of EGFR, and the ARHGEF11-NTRK1 was coexist with G12A mutation of KRAS. All of these five fusions were confirmed by FISH, while only the canonical TPM3-NTRK1 was confirmed by Oncomine Focus Assay. Conclusions: In summary, NTRK1 fusion is rare in lung adenocarcinoma and does not exist in squamous cell carcinoma or adenosquamous carcinoma cases. Age and gender are not significantly correlated with NTRK1 fusion. NTRK1 fusions were more common in non-smokers. Genomic DNA capture-based NGS can detect both canonical and noncanonical NTRK1 genomic rearrangements. Noncanonical NTRK1 genomic rearrangements need confirmed by other methods such as FISH. NTRK1 fusion may coexist with other canonical driver gene mutation.
Effect of body mass index and age on survival in patients with advanced lung cancer treated with anti-PD-1 immune checkpoint inhibitors.
Authors: Richard Corentin , Elkrief Arielle , Malo Julie , Cvetkovic Lena , Florescu Marie , Blais Normand , Tehfe Mustapha , Gagné Andréanne , Orain Michèle , Labbe Catherine , Joubert Philippe , Ghiringhelli François , Routy Bertrand 
Published: May 2019

e20676 Background: Age and body mass index (BMI) are important factors in patients treated with chemotherapy. However, in the era of immune checkpoint inhibitors (ICI), the importance of these baseline characteristics is unclear. For example, pooled analysis of age did not influence the clinical response to ICI, whereas patients with BMI > 35 had better outcomes in melanoma and renal cell carcinoma. More data are needed to clarify the role of these two characteristics in non-small cell lung cancer (NSCLC) patients amenable ICI. Methods: We conducted a retrospective analysis of patients treated with anti-PD1 ICI for advanced NSCLC at the Dijon Cancer Center (n = 177), University of Montreal University Hospital (n = 106) and Quebec Heart and Lung Institute (n = 98). BMI and age were considered as continuous or categorical variables. Patients’ baseline characteristics were compared using the Chi-squared test. Survival curves were estimated by the Kaplan-Meier method and compared with the Log-rank test in a univariate analysis. Multivariate cox regression model was used to determine hazard ratios and 95% confidence intervals for progression-free survival (PFS) and overall survival (OS) between the groups, adjusting for other clinicopathologic features. Results: Among 381 patients included, the median BMI was 24.5 (range 16.2-43.4) and 32.7% and 13.6% were classified as overweight or obese respectively. The median age was 66 (range 37-89) and 29% were older than 70 years-of-age. Considering BMI and age as continuous or categorical variables, they were not associated with PFS or OS, with the exception of BMI in the Dijon cohort (continuous: HR = 0.95, 95%CI[0.91-0.99]; < 25 vs > 25: HR = 0.68, 95%CI[0.47-0.99]). Subgroup analysis and multivariate cox regression did not reveal significant interaction of these two factors with outcomes. There was no difference in toxicity between the groups. ECOG performance status was the only significant factor in the three cohorts. Conclusions: Unlike previously described in the era of chemotherapy, obesity and age were not associated with outcomes in NSCLC patients treated with ICI.
Modeling causal associations between frailty components and mortality in older patients with cancer: A structural equation approach.
Authors: Canoui-Poitrine Florence , Martinez-Tapia Claudia , Pamoukdjian Frédéric , Mathoulin-Pélissier Simone , Frasca Matthieu , Paillaud Elena , Bringuier Michael , Brain Etienne , David Jean-Philippe , Laurent Marie , Bastuji-Garin Sylvie , Audureau Etienne 
Published: May 2019

e23021 Background: The independent prognostic value of both oncological and geriatric parameters is well-established in older cancer patients. Yet little is known about the causal pathways between them and how they may interact to affect mortality. Using structural equation modeling (SEM), we aimed to assess the direct and indirect impact of geriatric impairments and oncological parameters on mortality in older patients with cancer. Methods: Patients ≥70 years recruited in the ELCAPA cohort for geriatric assessment (GA), between 2007 and 2016, were included. The six following geriatric domains were assessed: function and mobility, nutrition, cognition, mood, comorbidities and polypharmacy, and social support. SEM analysis tested prespecified relationships between geriatric and oncological characteristics (i.e. stage, cancer site and anti-cancer treatment) and their influence on 6- and 12-months mortality following GA. Model fit was assessed through Root Mean Squared Error of Approximation (RMSEA) and Tucker-Lewis Index (TLI). Results: This analysis included 1434 patients (mean age, 80 years (±5.6); female, 48%; 48% metastasis; main localizations: colorectal (19%), upper digestive tract (17%), and breast (17%)). The 6- and 12-months mortality were 56% and 68%, respectively. Significant direct paths to increased mortality were identified for functional impairment (standardized coefficient (SC): 0.37; p < 0.001 and 0.32; p < 0.001), poor nutritional status (SC: 0.11; p = 0.005 and 0.14; p = 0.001) and poor social support (SC = 0.07; p = 0.08 and 0.09; p = 0.02), along with tumor site, metastatic status and anti-cancer treatment. SEM additionally revealed the indirect effects on mortality of comorbidities, cognitive impairment and depression mediated through functional and nutritional status. Model fit was excellent (RMSEA = 0.036, TLI = 0.941). Conclusions: SEM analysis showed the direct effects of functional and nutritional impairments on mortality and also revealed their central mediating role in the indirect impact of comorbidities, depression and cognitive impairment on mortality. Clinical trial information: NCT02884375.
Effects of a personal trainer led exercise intervention on physical activity and physical function of breast cancer survivors.
Authors: Wang Linda F. , Eaglehouse Yvonne L. , Poppenberg Janette T. , Brufsky Jill , Geramita Emily , Zhai Shuyan , Davis Kelliann , Gibbs Bethany , Metz Jason , Van Londen G J. 
Published: May 2019

e23053 Background: Regular exercise is an important tool to address physical and emotional effects of breast cancer treatment. However, many breast cancer survivors do not meet minimum recommended levels of physical activity. This study examines effects of a personal trainer led exercise intervention on physical activity levels and physical function in breast cancer survivors. Methods: Women who completed active treatment for breast cancer were recruited from oncology clinics and survivorship programs from September 2015-to September 2017. Subjects were randomized to an immediate exercise or a wait-list control group. The intervention included 3 personal training sessions over a period of up to 30 weeks. Physical activity and function were assessed before and after intervention by pedometer (7-day record) and endurance step test (steps in 2 minutes). Results: 60 women were randomized to immediate intervention (n = 31) or wait-list control (n = 29). Subjects were an average of (mean ± SD) 56 ± 10 years old and 2 ± 1 years since breast cancer diagnosis. At baseline, the exercise group averaged (mean ± SD) 5236 ± 2214 steps/day and 101 ± 23 steps on 2-minute step test while the control group averaged 5856 ± 2916 steps/day and 106 ± 23 steps on 2-minute step test. After intervention, change (mean ∆ ± SD) was 143 ± 1842 steps/day in the exercise group and 79 ± 1862 steps/day in the control group ( p= 0.9). On the 2-minute step test, the exercise group increased 18 ± 20 steps and the control group increased 9 ± 12 steps ( p= 0.07). Conclusions: While there was some improvement in physical function after the personal-trainer led intervention, the short duration and intensity of the intervention may have diminished the effects. Our results suggest a multi-faceted approach may be needed to support significant changes in breast cancer survivors’ physical activity. Future efforts employing a multidisciplinary team, which includes a certified personal trainer, and with larger patient samples may help address this possibility. Clinical trial information: NCT02770781.
Empaglifozin has cardioprotective and anti-inflammatory effects during doxorubicin treatment: A preclinical study.
Authors: Maurea Nicola , Quagliariello Vincenzo , Coppola Carmela , Rea Domenica , Barbieri Antonio , Arra Claudio , Botti Gerardo 
Published: May 2019

e23057 Background: Empagliflozin (EMPA), a selective inhibitor of the sodium glucose co-transporter 2 (SGLT2), reduces the risk of hospitalization for heart failure or cardiovascular death in type 2 diabetic patients. We aimed to study if EMPA could have cardioprotective and anti-inflammatory effects in Doxorubicin (DOXO) - Induced cardiotoxicity. Methods: we tested the effects of EMPA alone or in combination with DOXO in HL-1 adult cardiomyocytes evaluating: mitochondrial viability, lipid peroxidation, Leukotriene-B4 expression, p65-NF-κB activation and Interleukin 1β, 8 and 6 secretion. To evaluate cardiac function, Global Longitudinal Strain (GLS) were measured using 2D speckle tracking echocardiography in C57BL6 mice pretreated with EMPA (10 mg/kg/day) per os for 3 days. EMPA was then administered for additional 7 days, alone and in combination with DOXO (2.25 mg/kg/day ip). Cardiac lysates were processed for analysis of pro-inflammatory Interleukins. Results: EMPA, co-incubated with DOXO, is able to increase the cardiomyocyte viability of 33,6 and 82,3 % at 100 and 500 nM, respectively (compared to only DOXO treated cells). EMPA inhibits the lipid peroxidation by decreasing MDA and 4-HNA production of around 23,6 and 28,7 %, at 100 nM and of 47,8 and 52,1 % at 500 nM, respectively, compared to untreated cells. Moreover, EMPA has anti-inflammatory activity with a reduction of Leukotriene B4 expression and p65-NFkb activation of 58,4 and 64,3 % at 500 nM, respectively (compared to only DOXO treated cells). EMPA also decreased the expression of Interleukin 1β (of 28,5 and 68,8 %), Interleukin-8 (of 21,2 and 57,3 % ) and Interleukin-6 (of 28,1 and 49,8 %) at 100 and 500 nM, respectively, compared to only DOXO exposed cells. Preclinically, after 7 days with DOXO, GLS decreased. Interestingly, in mice treated with EMPA+DOXO, EMPA prevents the GLS’s reduction : GLS was 19.24 ± 1.5 (p < 0,01) vs DOXO alone. In DOXO-EMPA groups, the heart IL-1β, IL-6 and IL-8 tissue extract were reduced of 48, 54,4 and 58,2 % compared to only DOXO groups. Conclusions: EMPA has strong anti-inflammatory and cardioprotective effects in DOXO-Induced cardiotoxicity and these effects are mainly mediated by a reduction of the lipid peroxidation, Leukotriene-B4 and NF-κB activation.
Metastatic presentations of previously treated early stage breast cancer patients.
Authors: Itani Najla , Phadke Sneha Deepak , Grogan Nicole , Mott Sarah L 
Published: May 2019

e23065 Background: Breast cancer (BC) patients on surveillance often suffer from a fear of recurrence. Given that routine surveillance imaging is not recommended, the ability to recognize metastatic disease early on requires a knowledge of recurrence patterns. The aim of this study was to analyze the most common presentations of metastatic disease. Methods: A retrospective review was conducted of all adult patients at the Holden Comprehensive Cancer Center that were initially diagnosed with early stage BC and later developed metastatic disease, from 2000-2017. Chi-squared tests, and logistic and Cox regression models were used. Results: Of the 2,033 patient charts reviewed, 372 were deemed adequate for analysis. While most metastatic diagnoses were made as a result of reported symptoms (77.6%), 3.2% were made with clinical exam findings and 7.8% incidentally on imaging. Among those with symptoms, musculoskeletal pain was the most common (33.7%) and more frequently noted at scheduled (48.9%) compared to unscheduled visits (26%, p < 0.01). Receptor status was associated with nervous system (NS) symptoms at metastatic diagnosis (p = 0.01), with higher odds of NS symptoms in triple negative (TN) (OR = 3.0) and HER2+ cases compared to ER/PR+ HER2- cases (OR for ER/PR+ HER2+ = 3.5, OR for ER/PR- HER2+ = 3.8). Bone pain was not associated with any specific receptor subtype (p = 0.12). Initial stage and receptor status were associated with time to recurrence (TTR) (both p < 0.01), with stage III disease (versus stage I, HR = 1.60) and TNBC (versus [ER/PR+ HER2-, HR = 2.52) having the shortest TTR. On multivariable analysis, initial stage (p = 0.03), receptor status (p < 0.01), age (p < 0.01), and TTR (p < 0.01) were significantly associated with 10-year survival after metastatic diagnosis whereas the presence of symptoms at metastatic diagnosis was not (p = 0.27). Conclusions: Providers of patients on surveillance for a history of early stage breast cancer should modify their threshold of suspicion for recurrence depending on the characteristics of the initial diagnosis and symptoms subsequently reported. Although most metastatic recurrences were diagnosed by symptoms, patients did not necessarily have a shorter survival as a result of presenting with symptoms.